UA96942C2 - Похідні амінопіперидину як інгібітори бпхе (білка-переносника холестерилового ефіру) - Google Patents

Info

Publication number

UA96942C2

UA96942C2 UAA200813674A UAA200813674A UA96942C2 UA 96942 C2 UA96942 C2 UA 96942C2 UA A200813674 A UAA200813674 A UA A200813674A UA A200813674 A UAA200813674 A UA A200813674A UA 96942 C2 UA96942 C2 UA 96942C2

Authority

UA

Ukraine

Prior art keywords

mmol

mixture

alkyl

carboxylic acid

group

Prior art date

2006-07-20

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title 1
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical class NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 abstract description 170
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 38
• 201000010099 disease Diseases 0.000 abstract description 21
• 208000035475 disorder Diseases 0.000 abstract description 17
• 239000003112 inhibitor Substances 0.000 abstract description 12
• 230000005764 inhibitory process Effects 0.000 abstract description 11
• 230000001404 mediated effect Effects 0.000 abstract description 5
• KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 abstract 3
• 102100037637 Cholesteryl ester transfer protein Human genes 0.000 abstract 3
• 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 abstract 3
• 239000000203 mixture Substances 0.000 description 468
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 292
• -1 NZO3-- Chemical group 0.000 description 243
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 223
• 239000000243 solution Substances 0.000 description 210
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 200
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 172
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 166
• 230000014759 maintenance of location Effects 0.000 description 164
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 141
• 125000000217 alkyl group Chemical group 0.000 description 140
• 230000002829 reductive effect Effects 0.000 description 138
• 239000012044 organic layer Substances 0.000 description 116
• 230000015572 biosynthetic process Effects 0.000 description 115
• 235000019439 ethyl acetate Nutrition 0.000 description 102
• 238000003786 synthesis reaction Methods 0.000 description 101
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
• 125000000753 cycloalkyl group Chemical group 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 85
• 238000006243 chemical reaction Methods 0.000 description 83
• 239000003480 eluent Substances 0.000 description 83
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 81
• 239000012267 brine Substances 0.000 description 80
• 238000000034 method Methods 0.000 description 80
• 150000003839 salts Chemical class 0.000 description 77
• 125000003118 aryl group Chemical group 0.000 description 75
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 74
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 74
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
• 239000007864 aqueous solution Substances 0.000 description 67
• 229910052736 halogen Inorganic materials 0.000 description 64
• 239000000741 silica gel Substances 0.000 description 62
• 229910002027 silica gel Inorganic materials 0.000 description 62
• 238000003756 stirring Methods 0.000 description 61
• 125000002252 acyl group Chemical group 0.000 description 58
• 150000002367 halogens Chemical class 0.000 description 56
• 229920006395 saturated elastomer Polymers 0.000 description 55
• 125000003545 alkoxy group Chemical group 0.000 description 54
• 125000003277 amino group Chemical group 0.000 description 52
• 125000000623 heterocyclic group Chemical group 0.000 description 51
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 50
• 238000004587 chromatography analysis Methods 0.000 description 48
• 229910052739 hydrogen Inorganic materials 0.000 description 47
• 239000001257 hydrogen Substances 0.000 description 47
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
• 125000001424 substituent group Chemical group 0.000 description 45
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• 125000001072 heteroaryl group Chemical group 0.000 description 42
• 238000002307 isotope ratio mass spectrometry Methods 0.000 description 38
• 238000010898 silica gel chromatography Methods 0.000 description 35
• 125000001188 haloalkyl group Chemical group 0.000 description 34
• 239000000725 suspension Substances 0.000 description 32
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
• 239000010410 layer Substances 0.000 description 31
• 239000002253 acid Substances 0.000 description 30
• 125000003342 alkenyl group Chemical group 0.000 description 30
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
• 125000004093 cyano group Chemical group *C#N 0.000 description 29
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 125000003710 aryl alkyl group Chemical group 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 125000003302 alkenyloxy group Chemical group 0.000 description 24
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 150000002431 hydrogen Chemical class 0.000 description 23
• 239000012299 nitrogen atmosphere Substances 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 22
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
• 241000282414 Homo sapiens Species 0.000 description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 19
• 230000000694 effects Effects 0.000 description 19
• 239000008194 pharmaceutical composition Substances 0.000 description 19
• 238000002360 preparation method Methods 0.000 description 19
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• 239000003153 chemical reaction reagent Substances 0.000 description 18
• 239000003814 drug Substances 0.000 description 18
• 230000003287 optical effect Effects 0.000 description 18
• 239000004480 active ingredient Substances 0.000 description 17
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• 125000004432 carbon atom Chemical group C* 0.000 description 16
• 238000012746 preparative thin layer chromatography Methods 0.000 description 16
• 238000000746 purification Methods 0.000 description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
• 239000012298 atmosphere Substances 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
• 229940079593 drug Drugs 0.000 description 15
• 239000012634 fragment Substances 0.000 description 15
• 239000000651 prodrug Substances 0.000 description 15
• 229940002612 prodrug Drugs 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 238000004128 high performance liquid chromatography Methods 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
• DHVHORCFFOSRBP-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DHVHORCFFOSRBP-UHFFFAOYSA-N 0.000 description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
• 125000000000 cycloalkoxy group Chemical group 0.000 description 13
• 125000004663 dialkyl amino group Chemical group 0.000 description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 13
• 235000011181 potassium carbonates Nutrition 0.000 description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
• 150000004678 hydrides Chemical class 0.000 description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
• 235000019270 ammonium chloride Nutrition 0.000 description 11
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 11
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 11
• 238000006722 reduction reaction Methods 0.000 description 11
• 239000003826 tablet Substances 0.000 description 11
• 125000004149 thio group Chemical group *S* 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
• 239000012230 colorless oil Substances 0.000 description 10
• 208000029078 coronary artery disease Diseases 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 125000000524 functional group Chemical group 0.000 description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 10
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
• 102000015779 HDL Lipoproteins Human genes 0.000 description 9
• 108010010234 HDL Lipoproteins Proteins 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 150000007513 acids Chemical class 0.000 description 9
• 229910052799 carbon Inorganic materials 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 9
• 239000011780 sodium chloride Substances 0.000 description 9
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
• 102000007330 LDL Lipoproteins Human genes 0.000 description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 8
• 238000004440 column chromatography Methods 0.000 description 8
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 8
• 206010012601 diabetes mellitus Diseases 0.000 description 8
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 8
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 238000007254 oxidation reaction Methods 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• 238000010561 standard procedure Methods 0.000 description 8
• 229940123338 Aldosterone synthase inhibitor Drugs 0.000 description 7
• 206010003210 Arteriosclerosis Diseases 0.000 description 7
• 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 7
• 108091034117 Oligonucleotide Proteins 0.000 description 7
• 208000018262 Peripheral vascular disease Diseases 0.000 description 7
• 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 7
• 108010062497 VLDL Lipoproteins Proteins 0.000 description 7
• 230000029936 alkylation Effects 0.000 description 7
• 238000005804 alkylation reaction Methods 0.000 description 7
• 208000011775 arteriosclerosis disease Diseases 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
• 201000001386 familial hypercholesterolemia Diseases 0.000 description 7
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 6
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• 206010007559 Cardiac failure congestive Diseases 0.000 description 6
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• 206010019280 Heart failures Diseases 0.000 description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 239000013543 active substance Substances 0.000 description 6
• 125000002619 bicyclic group Chemical group 0.000 description 6
• 239000006172 buffering agent Substances 0.000 description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
• 238000005516 engineering process Methods 0.000 description 6
• LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 239000011572 manganese Substances 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 230000003647 oxidation Effects 0.000 description 6
• 229920000642 polymer Polymers 0.000 description 6
• 239000003755 preservative agent Substances 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 6
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
• 238000000844 transformation Methods 0.000 description 6
• ATLQGZVLWOURFU-UHFFFAOYSA-N 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(CBr)=CC(C(F)(F)F)=C1 ATLQGZVLWOURFU-UHFFFAOYSA-N 0.000 description 5
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
• QZAQRNWUUISOMS-UHFFFAOYSA-N 4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-2-ethylpiperidine-1-carboxylic acid Chemical compound FC(C=1C=C(CNC2CC(N(CC2)C(=O)O)CC)C=C(C=1)C(F)(F)F)(F)F QZAQRNWUUISOMS-UHFFFAOYSA-N 0.000 description 5
• XQABVLBGNWBWIV-UHFFFAOYSA-N 4-methoxypyridine Chemical compound COC1=CC=NC=C1 XQABVLBGNWBWIV-UHFFFAOYSA-N 0.000 description 5
• 239000005541 ACE inhibitor Substances 0.000 description 5
• 208000031226 Hyperlipidaemia Diseases 0.000 description 5
• 206010020772 Hypertension Diseases 0.000 description 5
• 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 5
• 102000004895 Lipoproteins Human genes 0.000 description 5
• 108090001030 Lipoproteins Proteins 0.000 description 5
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 125000000304 alkynyl group Chemical group 0.000 description 5
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 235000012000 cholesterol Nutrition 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 150000004820 halides Chemical group 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• 208000010125 myocardial infarction Diseases 0.000 description 5
• 125000001624 naphthyl group Chemical group 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 238000002953 preparative HPLC Methods 0.000 description 5
• URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 239000011975 tartaric acid Substances 0.000 description 5
• 235000002906 tartaric acid Nutrition 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 4
• MVPJBAOWMRBIIJ-UHFFFAOYSA-N 2,6-diethyl-4-oxopiperidine-1-carboxylic acid Chemical compound C(C)C1N(C(CC(C1)=O)CC)C(=O)O MVPJBAOWMRBIIJ-UHFFFAOYSA-N 0.000 description 4
• NYFRPECWXWWELE-UHFFFAOYSA-N 2-ethyl-4-oxo-2,3-dihydropyridine-1-carboxylic acid Chemical compound CCC1CC(=O)C=CN1C(O)=O NYFRPECWXWWELE-UHFFFAOYSA-N 0.000 description 4
• GQKYULAWTKKWQP-UHFFFAOYSA-N 4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-2,6-diethylpiperidine-1-carboxylic acid Chemical compound FC(C=1C=C(CNC2CC(N(C(C2)CC)C(=O)O)CC)C=C(C=1)C(F)(F)F)(F)F GQKYULAWTKKWQP-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
• 208000032928 Dyslipidaemia Diseases 0.000 description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
• 208000035150 Hypercholesterolemia Diseases 0.000 description 4
• 206010021024 Hypolipidaemia Diseases 0.000 description 4
• 108010028554 LDL Cholesterol Proteins 0.000 description 4
• 238000008214 LDL Cholesterol Methods 0.000 description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 description 4
• 208000008589 Obesity Diseases 0.000 description 4
• 108090000854 Oxidoreductases Proteins 0.000 description 4
• 102000004316 Oxidoreductases Human genes 0.000 description 4
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 125000003282 alkyl amino group Chemical group 0.000 description 4
• 125000005907 alkyl ester group Chemical group 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 150000001450 anions Chemical class 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 239000011575 calcium Substances 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
• 125000004122 cyclic group Chemical group 0.000 description 4
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 229940093915 gynecological organic acid Drugs 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 208000006575 hypertriglyceridemia Diseases 0.000 description 4
• 208000029498 hypoalphalipoproteinemia Diseases 0.000 description 4
• 150000002466 imines Chemical class 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 230000004060 metabolic process Effects 0.000 description 4
• 239000004530 micro-emulsion Substances 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 235000020824 obesity Nutrition 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 235000005985 organic acids Nutrition 0.000 description 4
• 150000007530 organic bases Chemical class 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000010926 purge Methods 0.000 description 4
• 238000006268 reductive amination reaction Methods 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• 230000002792 vascular Effects 0.000 description 4
• SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 3
• OVXSCGOQXMPFMA-GHMZBOCLSA-N (2R,6R)-4-oxo-2,6-di(propan-2-yl)piperidine-1-carboxylic acid Chemical compound C(C)(C)[C@@H]1N([C@H](CC(C1)=O)C(C)C)C(=O)O OVXSCGOQXMPFMA-GHMZBOCLSA-N 0.000 description 3
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 3
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• DWXPOGQMJSSFCZ-UHFFFAOYSA-N 1-(bromomethyl)-3-chloro-5-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(Cl)=CC(CBr)=C1 DWXPOGQMJSSFCZ-UHFFFAOYSA-N 0.000 description 3
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 3
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
• LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 3
• 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 3
• ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical class O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 3
• UUXLULSSTZVOCZ-UHFFFAOYSA-N 4,4-diethylpiperidine-1-carboxylic acid Chemical compound C(C)C1(CCN(CC1)C(=O)O)CC UUXLULSSTZVOCZ-UHFFFAOYSA-N 0.000 description 3
• JEQZSHGWVDXLKA-UHFFFAOYSA-N 4-(4-bromoanilino)-2-ethylpiperidine-1-carboxylic acid Chemical compound BrC1=CC=C(C=C1)NC1CC(N(CC1)C(=O)O)CC JEQZSHGWVDXLKA-UHFFFAOYSA-N 0.000 description 3
• HDOKOEOSJBWVJY-UHFFFAOYSA-N 4-(cyclohexylamino)-2-ethylpiperidine-1-carboxylic acid Chemical compound C1(CCCCC1)NC1CC(N(CC1)C(=O)O)CC HDOKOEOSJBWVJY-UHFFFAOYSA-N 0.000 description 3
• JZNSKFGVLMOJGB-UHFFFAOYSA-N 4-oxo-2-propan-2-yl-2,3-dihydropyridine-1-carboxylic acid Chemical compound C(C)(C)C1N(C=CC(C1)=O)C(=O)O JZNSKFGVLMOJGB-UHFFFAOYSA-N 0.000 description 3
• XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 3
• PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 3
• PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 3
• 206010002383 Angina Pectoris Diseases 0.000 description 3
• 241000283725 Bos Species 0.000 description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
• 229940127291 Calcium channel antagonist Drugs 0.000 description 3
• 241000282472 Canis lupus familiaris Species 0.000 description 3
• 102000014914 Carrier Proteins Human genes 0.000 description 3
• 108010078791 Carrier Proteins Proteins 0.000 description 3
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 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
• 108010010803 Gelatin Proteins 0.000 description 3
• 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 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
• 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• 206010063837 Reperfusion injury Diseases 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 208000007536 Thrombosis Diseases 0.000 description 3
• 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 3
• UONWUJGPXCGHNL-UHFFFAOYSA-N [3-amino-5-(trifluoromethyl)phenyl]methanol Chemical compound NC1=CC(CO)=CC(C(F)(F)F)=C1 UONWUJGPXCGHNL-UHFFFAOYSA-N 0.000 description 3
• 229960002478 aldosterone Drugs 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
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
• 229960000528 amlodipine Drugs 0.000 description 3
• ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 3
• 238000002399 angioplasty Methods 0.000 description 3
• 125000004104 aryloxy group Chemical group 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• 239000000480 calcium channel blocker Substances 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 238000004296 chiral HPLC Methods 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• 239000002299 complementary DNA Substances 0.000 description 3
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 238000013504 emergency use authorization Methods 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 235000003599 food sweetener Nutrition 0.000 description 3
• 238000001640 fractional crystallisation Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 229940015043 glyoxal Drugs 0.000 description 3
• 125000004438 haloalkoxy group Chemical group 0.000 description 3
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000002883 imidazolyl group Chemical group 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
• 208000028867 ischemia Diseases 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 150000002632 lipids Chemical class 0.000 description 3
• 229910052744 lithium Inorganic materials 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
• 239000011976 maleic acid Substances 0.000 description 3
• 239000001630 malic acid Substances 0.000 description 3
• 235000011090 malic acid Nutrition 0.000 description 3
• 229940126601 medicinal product Drugs 0.000 description 3
• 229940098779 methanesulfonic acid Drugs 0.000 description 3
• 208000031225 myocardial ischemia Diseases 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 125000006684 polyhaloalkyl group Polymers 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 239000002461 renin inhibitor Substances 0.000 description 3
• 229940086526 renin-inhibitors Drugs 0.000 description 3
• 208000037803 restenosis Diseases 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 235000009518 sodium iodide Nutrition 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 230000003637 steroidlike Effects 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 125000000565 sulfonamide group Chemical group 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000003765 sweetening agent Substances 0.000 description 3
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
• 125000000335 thiazolyl group Chemical group 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 150000003626 triacylglycerols Chemical class 0.000 description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
• 229960001722 verapamil Drugs 0.000 description 3
• HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
• HEHLOWOOVUULKX-UHFFFAOYSA-N (4-methylphenyl)methanesulfinic acid Chemical compound CC1=CC=C(CS(O)=O)C=C1 HEHLOWOOVUULKX-UHFFFAOYSA-N 0.000 description 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 2
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
• PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 2
• HMVSKKRMOPJKLU-UHFFFAOYSA-N 1-(bromomethyl)-3-chloro-5-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC(Cl)=CC(CBr)=C1 HMVSKKRMOPJKLU-UHFFFAOYSA-N 0.000 description 2
• HUXGOSMQAOCVGE-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxy-5-(trifluoromethyl)benzene Chemical compound COC1=CC(CBr)=CC(C(F)(F)F)=C1 HUXGOSMQAOCVGE-UHFFFAOYSA-N 0.000 description 2
• OOVFAAFQABNXLS-UHFFFAOYSA-N 1-[3-(bromomethyl)-5-(trifluoromethyl)phenyl]-5-methyltetrazole Chemical compound CC1=NN=NN1C1=CC(CBr)=CC(C(F)(F)F)=C1 OOVFAAFQABNXLS-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
• AHECQDFFSXYDJT-UHFFFAOYSA-N 2,6-diethyl-4-[(5-hydroxypyrimidin-2-yl)amino]piperidine-1-carboxylic acid Chemical compound C(C)C1N(C(CC(C1)NC1=NC=C(C=N1)O)CC)C(=O)O AHECQDFFSXYDJT-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
• MBKACHADOOBNCF-UHFFFAOYSA-N 2-ethyl-4-oxopiperidine-1-carboxylic acid Chemical compound CCC1CC(=O)CCN1C(O)=O MBKACHADOOBNCF-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• WMKYKQWKLILFBM-UHFFFAOYSA-N 2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CC=CC=C1 WMKYKQWKLILFBM-UHFFFAOYSA-N 0.000 description 2
• WAKMMQSMEDJRRI-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC(C(Cl)=O)=CC(C(F)(F)F)=C1 WAKMMQSMEDJRRI-UHFFFAOYSA-N 0.000 description 2
• XCQHEKDHXNEMLW-UHFFFAOYSA-N 3-(chloromethyl)-n,n-dimethyl-5-(trifluoromethyl)aniline Chemical compound CN(C)C1=CC(CCl)=CC(C(F)(F)F)=C1 XCQHEKDHXNEMLW-UHFFFAOYSA-N 0.000 description 2
• VAQSHRZOMRFBCX-UHFFFAOYSA-N 3-methoxy-5-(trifluoromethyl)benzoic acid Chemical compound COC1=CC(C(O)=O)=CC(C(F)(F)F)=C1 VAQSHRZOMRFBCX-UHFFFAOYSA-N 0.000 description 2
• UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 2
• CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 2
• UNYSEEUVFCINOW-UHFFFAOYSA-N 4-acetyloxycyclohexane-1-carboxylic acid Chemical compound CC(=O)OC1CCC(C(O)=O)CC1 UNYSEEUVFCINOW-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 102000008873 Angiotensin II receptor Human genes 0.000 description 2
• 108050000824 Angiotensin II receptor Proteins 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 108010061435 Enalapril Proteins 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 108010023302 HDL Cholesterol Proteins 0.000 description 2
• 241000581652 Hagenia abyssinica Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 108010007622 LDL Lipoproteins Proteins 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 238000006683 Mannich reaction Methods 0.000 description 2
• FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 102000003729 Neprilysin Human genes 0.000 description 2
• 108090000028 Neprilysin Proteins 0.000 description 2
• ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-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
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 241000159610 Roya <green alga> Species 0.000 description 2
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• WRLQDVAAXZHUTK-UHFFFAOYSA-N [3-(dimethylamino)-5-(trifluoromethyl)phenyl]methanol Chemical compound CN(C)C1=CC(CO)=CC(C(F)(F)F)=C1 WRLQDVAAXZHUTK-UHFFFAOYSA-N 0.000 description 2
• MPYFWGBMAYFJOH-UHFFFAOYSA-N [3-bromo-5-(trifluoromethyl)phenyl]methanol Chemical compound OCC1=CC(Br)=CC(C(F)(F)F)=C1 MPYFWGBMAYFJOH-UHFFFAOYSA-N 0.000 description 2
• ROACFQURKLEGKL-UHFFFAOYSA-N [3-methoxy-5-(trifluoromethyl)phenyl]methanol Chemical compound COC1=CC(CO)=CC(C(F)(F)F)=C1 ROACFQURKLEGKL-UHFFFAOYSA-N 0.000 description 2
• HBIQLOSUNLJCEF-UHFFFAOYSA-N [3-methylsulfonyl-5-(trifluoromethyl)phenyl]methanol Chemical compound CS(=O)(=O)C1=CC(CO)=CC(C(F)(F)F)=C1 HBIQLOSUNLJCEF-UHFFFAOYSA-N 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 150000001325 aldosterones Chemical class 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 238000005576 amination reaction Methods 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 239000003886 aromatase inhibitor Substances 0.000 description 2
• 229960004530 benazepril Drugs 0.000 description 2
• KKBIUAUSZKGNOA-HNAYVOBHSA-N benzyl (2s)-2-[[(2s)-2-(acetylsulfanylmethyl)-3-(1,3-benzodioxol-5-yl)propanoyl]amino]propanoate Chemical compound O=C([C@@H](NC(=O)[C@@H](CSC(C)=O)CC=1C=C2OCOC2=CC=1)C)OCC1=CC=CC=C1 KKBIUAUSZKGNOA-HNAYVOBHSA-N 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 229910000085 borane Inorganic materials 0.000 description 2
• NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-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
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 239000012141 concentrate Substances 0.000 description 2
• 235000008504 concentrate Nutrition 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• 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 2
• 238000006900 dealkylation reaction Methods 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• 238000010908 decantation Methods 0.000 description 2
• 238000000354 decomposition reaction Methods 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 125000004982 dihaloalkyl group Chemical group 0.000 description 2
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 2
• 229960004166 diltiazem Drugs 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
• DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
• 239000002934 diuretic Substances 0.000 description 2
• 230000001882 diuretic effect Effects 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 239000000890 drug combination Substances 0.000 description 2
• 230000009977 dual effect Effects 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 229960000873 enalapril Drugs 0.000 description 2
• GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 2
• 238000003821 enantio-separation Methods 0.000 description 2
• 239000002308 endothelin receptor antagonist Substances 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 229950011548 fadrozole Drugs 0.000 description 2
• 229950005203 fasidotril Drugs 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229960003765 fluvastatin Drugs 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 235000010855 food raising agent Nutrition 0.000 description 2
• 239000001530 fumaric acid Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 125000004470 heterocyclooxy group Chemical group 0.000 description 2
• 229960002003 hydrochlorothiazide Drugs 0.000 description 2
• 230000003301 hydrolyzing effect Effects 0.000 description 2
• 230000033444 hydroxylation Effects 0.000 description 2
• 238000005805 hydroxylation reaction Methods 0.000 description 2
• 150000003949 imides Chemical class 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 229960004427 isradipine Drugs 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 238000006138 lithiation reaction Methods 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
• 210000004185 liver Anatomy 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 159000000003 magnesium salts Chemical class 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 2
• UFQSTBGEWZUCBQ-UHFFFAOYSA-M magnesium;methanidylcyclohexane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1CCCCC1 UFQSTBGEWZUCBQ-UHFFFAOYSA-M 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 2
• IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 2
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 2
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000006682 monohaloalkyl group Chemical group 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 229960001783 nicardipine Drugs 0.000 description 2
• HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
• 229960001597 nifedipine Drugs 0.000 description 2
• 229960000715 nimodipine Drugs 0.000 description 2
• 229960000227 nisoldipine Drugs 0.000 description 2
• 229960005425 nitrendipine Drugs 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 125000000160 oxazolidinyl group Chemical group 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
• 150000003053 piperidines Chemical class 0.000 description 2
• 229960002797 pitavastatin Drugs 0.000 description 2
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
• 235000019345 sodium thiosulphate Nutrition 0.000 description 2
• 239000002594 sorbent Substances 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• 239000010936 titanium Substances 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 229960004699 valsartan Drugs 0.000 description 2
• SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 230000003313 weakening effect Effects 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
• RBPHBLDGMYKMKY-BDVNFPICSA-N (2R,3R,4R,5S)-6-(methoxyamino)hexane-1,2,3,4,5-pentol Chemical compound CONC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO RBPHBLDGMYKMKY-BDVNFPICSA-N 0.000 description 1
• DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• BAVDEDVBIHTHJQ-UVJOBNTFSA-N (2s)-1-[(2s)-6-amino-2-[[(1s)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid;hydrate Chemical compound O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 BAVDEDVBIHTHJQ-UVJOBNTFSA-N 0.000 description 1
• BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
• ZGGHKIMDNBDHJB-RPQBTBOMSA-M (3S,5R)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@H](O)C[C@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-RPQBTBOMSA-M 0.000 description 1
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
• QXKWLTWUJXGNHI-UHFFFAOYSA-N (4-octan-2-yloxycarbonylphenyl) 4-(4-octylphenyl)benzoate Chemical compound C1=CC(CCCCCCCC)=CC=C1C1=CC=C(C(=O)OC=2C=CC(=CC=2)C(=O)OC(C)CCCCCC)C=C1 QXKWLTWUJXGNHI-UHFFFAOYSA-N 0.000 description 1
• SVJMLYUFVDMUHP-XIFFEERXSA-N (4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-[3-(4,4-diphenyl-1-piperidinyl)propyl] ester O3-methyl ester Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OCCCN2CCC(CC2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC([N+]([O-])=O)=C1 SVJMLYUFVDMUHP-XIFFEERXSA-N 0.000 description 1
• VDSBXXDKCUBMQC-HNGSOEQISA-N (4r,6s)-6-[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohexen-1-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C1=C(F)C(C)=CC(C=2CC(C)(C)CC(C)(C)C=2\C=C\[C@H]2OC(=O)C[C@H](O)C2)=C1 VDSBXXDKCUBMQC-HNGSOEQISA-N 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
• UDVPQRRWUGKGQY-XQHVRGAUSA-N (e)-but-2-enal Chemical compound C\C=C\C=O.C\C=C\C=O UDVPQRRWUGKGQY-XQHVRGAUSA-N 0.000 description 1
• GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• FRUWDTKBOVGJKF-UHFFFAOYSA-N 1-(bromomethyl)-3-methylsulfonyl-5-(trifluoromethyl)benzene Chemical compound CS(=O)(=O)C1=CC(CBr)=CC(C(F)(F)F)=C1 FRUWDTKBOVGJKF-UHFFFAOYSA-N 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• IIEQJSIHKZXTHY-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethoxymethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCOCOC(=O)C(C)(C)C IIEQJSIHKZXTHY-UHFFFAOYSA-N 0.000 description 1
• CZLVPINBLDRZCJ-UHFFFAOYSA-N 2,3,4,4,5,5,6,6-octachlorocyclohex-2-en-1-one Chemical compound ClC1=C(Cl)C(Cl)(Cl)C(Cl)(Cl)C(Cl)(Cl)C1=O CZLVPINBLDRZCJ-UHFFFAOYSA-N 0.000 description 1
• 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• PKRIOQNSNITQNL-UHFFFAOYSA-N 2,6-diethylpiperidine-1-carboxylic acid Chemical compound C(C)C1N(C(CCC1)CC)C(=O)O PKRIOQNSNITQNL-UHFFFAOYSA-N 0.000 description 1
• VYJUHCOBOXKPDU-UHFFFAOYSA-N 2-(2-oxoethyl)piperidine-1-carboxylic acid Chemical compound OC(=O)N1CCCCC1CC=O VYJUHCOBOXKPDU-UHFFFAOYSA-N 0.000 description 1
• QWMPLIYRMZRQNJ-UHFFFAOYSA-N 2-(cyclohexylmethyl)-4-oxo-2,3-dihydropyridine-1-carboxylic acid Chemical compound C1(CCCCC1)CC1N(C=CC(C1)=O)C(=O)O QWMPLIYRMZRQNJ-UHFFFAOYSA-N 0.000 description 1
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• RRKASFBTGYTDBM-UHFFFAOYSA-N 2-benzyl-4-[(4-ethoxycarbonyl-1,3-oxazol-2-yl)amino]-6-ethylpiperidine-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)C1N(C(CC(C1)NC=1OC=C(N=1)C(=O)OCC)CC)C(=O)O RRKASFBTGYTDBM-UHFFFAOYSA-N 0.000 description 1
• OBISUASDTDRGMT-UHFFFAOYSA-N 2-benzyl-4-[(5-bromopyrimidin-2-yl)amino]-6-ethylpiperidine-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)C1N(C(CC(C1)NC1=NC=C(C=N1)Br)CC)C(=O)O OBISUASDTDRGMT-UHFFFAOYSA-N 0.000 description 1
• FVLCZKRFRDSVFQ-UHFFFAOYSA-N 2-benzyl-4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-6-(hydroxymethyl)piperidine-1-carboxylic acid Chemical compound C1C(CC(N(C1CC2=CC=CC=C2)C(=O)O)CO)NCC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F FVLCZKRFRDSVFQ-UHFFFAOYSA-N 0.000 description 1
• HURKDELVSVWDMJ-UHFFFAOYSA-N 2-benzyl-4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-6-ethylpiperidine-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)C1N(C(CC(C1)NCC1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)CC)C(=O)O HURKDELVSVWDMJ-UHFFFAOYSA-N 0.000 description 1
• OSHJOVBZRIOARW-UHFFFAOYSA-N 2-benzyl-4-oxo-2,3-dihydropyridine-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)C1N(C=CC(C1)=O)C(=O)O OSHJOVBZRIOARW-UHFFFAOYSA-N 0.000 description 1
• DTIXFSVKVVMURX-UHFFFAOYSA-N 2-benzyl-6-ethyl-4-oxopiperidine-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)C1N(C(CC(C1)=O)CC)C(=O)O DTIXFSVKVVMURX-UHFFFAOYSA-N 0.000 description 1
• PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 1
• AFZJELJKFJSQGN-UHFFFAOYSA-N 2-chloro-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(Cl)=N1 AFZJELJKFJSQGN-UHFFFAOYSA-N 0.000 description 1
• JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
• NILLIUYSJFTTRH-UHFFFAOYSA-N 2-cyclopentylacetyl chloride Chemical compound ClC(=O)CC1CCCC1 NILLIUYSJFTTRH-UHFFFAOYSA-N 0.000 description 1
• DXTWXKMIQDKQIG-UHFFFAOYSA-N 2-ethyl-6-(methoxymethyl)-4-oxopiperidine-1-carboxylic acid Chemical compound C(C)C1N(C(CC(C1)=O)COC)C(=O)O DXTWXKMIQDKQIG-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
• LSYXNECZRAJSMM-UHFFFAOYSA-N 2-methyl-4-oxopiperidine-1-carboxylic acid Chemical compound CC1CC(=O)CCN1C(O)=O LSYXNECZRAJSMM-UHFFFAOYSA-N 0.000 description 1
• 125000004810 2-methylpropylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:2])C([H])([H])[*:1] 0.000 description 1
• KFTYFTKODBWKOU-UHFFFAOYSA-N 2-methylsulfonylethanol Chemical compound CS(=O)(=O)CCO KFTYFTKODBWKOU-UHFFFAOYSA-N 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• 125000006087 2-oxopyrrolodinyl group Chemical group 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 description 1
• WBTHOSZMTIPJLR-UHFFFAOYSA-N 3-amino-5-(trifluoromethyl)benzoic acid Chemical compound NC1=CC(C(O)=O)=CC(C(F)(F)F)=C1 WBTHOSZMTIPJLR-UHFFFAOYSA-N 0.000 description 1
• MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• AMZBKZQMAZWIJM-UHFFFAOYSA-N 3-bromo-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(C(F)(F)F)=C1 AMZBKZQMAZWIJM-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• ODCLHXGXGFBBTA-UHFFFAOYSA-N 3-nitro-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 ODCLHXGXGFBBTA-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• UFORYRVGIFXPRV-UHFFFAOYSA-N 4-[(4-ethoxycarbonyl-1,3-oxazol-2-yl)amino]-2,6-diethylpiperidine-1-carboxylic acid Chemical compound C(C)OC(=O)C=1N=C(OC=1)NC1CC(N(C(C1)CC)C(=O)O)CC UFORYRVGIFXPRV-UHFFFAOYSA-N 0.000 description 1
• VRDCFSHMPGJARO-UHFFFAOYSA-N 4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-2-ethyl-6-(methoxymethyl)piperidine-1-carboxylic acid Chemical compound FC(C=1C=C(CNC2CC(N(C(C2)COC)C(=O)O)CC)C=C(C1)C(F)(F)F)(F)F VRDCFSHMPGJARO-UHFFFAOYSA-N 0.000 description 1
• PGMMOYGURCAKKL-UHFFFAOYSA-N 4-amino-2,6-diethylpiperidine-1-carboxylic acid Chemical compound NC1CC(N(C(C1)CC)C(=O)O)CC PGMMOYGURCAKKL-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• GYCPLYCTMDTEPU-UHFFFAOYSA-N 5-bromopyrimidine Chemical compound BrC1=CN=CN=C1 GYCPLYCTMDTEPU-UHFFFAOYSA-N 0.000 description 1
• RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
• RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 244000005894 Albizia lebbeck Species 0.000 description 1
• JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 206010059245 Angiopathy Diseases 0.000 description 1
• 102000005862 Angiotensin II Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• 108010064733 Angiotensins Proteins 0.000 description 1
• 102000015427 Angiotensins Human genes 0.000 description 1
• 241000256844 Apis mellifera Species 0.000 description 1
• 101500021173 Aplysia californica Myomodulin-E Proteins 0.000 description 1
• 101150102415 Apob gene Proteins 0.000 description 1
• 101710095342 Apolipoprotein B Proteins 0.000 description 1
• 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
• 101100327837 Arabidopsis thaliana CHLH gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241001167018 Aroa Species 0.000 description 1
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
• 229940122815 Aromatase inhibitor Drugs 0.000 description 1
• CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 241000271566 Aves Species 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
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
• 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• IFYLTXNCFVRALQ-OALUTQOASA-N Ceronapril Chemical compound O([C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)P(O)(=O)CCCCC1=CC=CC=C1 IFYLTXNCFVRALQ-OALUTQOASA-N 0.000 description 1
• 241000283153 Cetacea Species 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 208000016998 Conn syndrome Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 240000008840 Dalbergia sissoo Species 0.000 description 1
• 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 description 1
• 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 238000006228 Dieckmann condensation reaction Methods 0.000 description 1
• 238000005698 Diels-Alder reaction Methods 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 239000005977 Ethylene Chemical group 0.000 description 1
• 102000020897 Formins Human genes 0.000 description 1
• 108091022623 Formins Proteins 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 244000194101 Ginkgo biloba Species 0.000 description 1
• 235000008100 Ginkgo biloba Nutrition 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• 108010015899 Glycopeptides Proteins 0.000 description 1
• 102000002068 Glycopeptides Human genes 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101000874160 Homo sapiens Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 208000001953 Hypotension Diseases 0.000 description 1
• 108010093096 Immobilized Enzymes Proteins 0.000 description 1
• 206010061216 Infarction Diseases 0.000 description 1
• 238000006043 Intramolecular Michael addition reaction Methods 0.000 description 1
• 238000005577 Kumada cross-coupling reaction Methods 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• 108010007859 Lisinopril Proteins 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241000699673 Mesocricetus auratus Species 0.000 description 1
• CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 description 1
• HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 229910016006 MoSi Inorganic materials 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 101001031591 Mus musculus Heart- and neural crest derivatives-expressed protein 2 Proteins 0.000 description 1
• 101100237844 Mus musculus Mmp19 gene Proteins 0.000 description 1
• CAUBWLYZCDDYEF-UHFFFAOYSA-N N-Nitroso-N-methylurethane Chemical compound CCOC(=O)N(C)N=O CAUBWLYZCDDYEF-UHFFFAOYSA-N 0.000 description 1
• 241001611408 Nebo Species 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• CVRALZAYCYJELZ-UHFFFAOYSA-N O-(4-bromo-2,5-dichlorophenyl) O-methyl phenylphosphonothioate Chemical compound C=1C=CC=CC=1P(=S)(OC)OC1=CC(Cl)=C(Br)C=C1Cl CVRALZAYCYJELZ-UHFFFAOYSA-N 0.000 description 1
• 101150091025 Oda gene Proteins 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 241000370985 Parides Species 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 241000269435 Rana <genus> Species 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 229940123934 Reductase inhibitor Drugs 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 239000005478 Saprisartan Substances 0.000 description 1
• DUEWVPTZCSAMNB-UHFFFAOYSA-N Saprisartan Chemical compound NC(=O)C=1N(CC=2C=C3C(Br)=C(OC3=CC=2)C=2C(=CC=CC=2)NS(=O)(=O)C(F)(F)F)C(CC)=NC=1C1CC1 DUEWVPTZCSAMNB-UHFFFAOYSA-N 0.000 description 1
• 241000242678 Schistosoma Species 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
• 108010054082 Sterol O-acyltransferase Proteins 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
• UATJOMSPNYCXIX-UHFFFAOYSA-N Trinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 UATJOMSPNYCXIX-UHFFFAOYSA-N 0.000 description 1
• PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• VXDSGTRNDFHIJB-QQPOVDNESA-N [(1s,4ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1CCC[C@@H](C21)OC(=O)[C@@H](C)CC)=CC(C)C2CC[C@@H]1C[C@@H](O)CC(=O)O1 VXDSGTRNDFHIJB-QQPOVDNESA-N 0.000 description 1
• PZHLQGDDGUWVKH-UHFFFAOYSA-N [3-chloro-5-(trifluoromethoxy)phenyl]methanol Chemical compound OCC1=CC(Cl)=CC(OC(F)(F)F)=C1 PZHLQGDDGUWVKH-UHFFFAOYSA-N 0.000 description 1
• RKFJLAMKBRRYJG-UHFFFAOYSA-M [Br-].[Mg+]CCC1=CC=CC=C1 Chemical compound [Br-].[Mg+]CCC1=CC=CC=C1 RKFJLAMKBRRYJG-UHFFFAOYSA-M 0.000 description 1
• CWGJBBRZFIPXNZ-UHFFFAOYSA-N [C-]#N.Br Chemical compound [C-]#N.Br CWGJBBRZFIPXNZ-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 238000007171 acid catalysis Methods 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 125000004442 acylamino group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 239000002170 aldosterone antagonist Substances 0.000 description 1
• 229940083712 aldosterone antagonist Drugs 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• HZVVJJIYJKGMFL-UHFFFAOYSA-N almasilate Chemical compound O.[Mg+2].[Al+3].[Al+3].O[Si](O)=O.O[Si](O)=O HZVVJJIYJKGMFL-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229960002932 anastrozole Drugs 0.000 description 1
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• PHFDAOXXIZOUIX-UHFFFAOYSA-N anipamil Chemical compound C=1C=CC(OC)=CC=1C(CCCCCCCCCCCC)(C#N)CCCN(C)CCC1=CC=CC(OC)=C1 PHFDAOXXIZOUIX-UHFFFAOYSA-N 0.000 description 1
• 229950011530 anipamil Drugs 0.000 description 1
• 230000003288 anthiarrhythmic effect Effects 0.000 description 1
• 230000003257 anti-anginal effect Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 239000003416 antiarrhythmic agent Substances 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 229910052785 arsenic Inorganic materials 0.000 description 1
• RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 239000000305 astragalus gummifer gum Substances 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 239000003899 bactericide agent Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 229960004067 benazeprilat Drugs 0.000 description 1
• MADRIHWFJGRSBP-ROUUACIJSA-N benazeprilat Chemical compound C([C@H](N[C@H]1CCC2=CC=CC=C2N(C1=O)CC(=O)O)C(O)=O)CC1=CC=CC=C1 MADRIHWFJGRSBP-ROUUACIJSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000005870 benzindolyl group Chemical group 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
• 239000012965 benzophenone Substances 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 229910052790 beryllium Inorganic materials 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 229960003065 bosentan Drugs 0.000 description 1
• SXTRWVVIEPWAKM-UHFFFAOYSA-N bosentan hydrate Chemical compound O.COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SXTRWVVIEPWAKM-UHFFFAOYSA-N 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• ZJRWDIJRKKXMNW-UHFFFAOYSA-N carbonic acid;cobalt Chemical compound [Co].OC(O)=O ZJRWDIJRKKXMNW-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000013339 cereals Nutrition 0.000 description 1
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
• 229960005110 cerivastatin Drugs 0.000 description 1
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
• GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
• 229950005749 ceronapril Drugs 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 230000009920 chelation Effects 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 229960002155 chlorothiazide Drugs 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 229960001523 chlortalidone Drugs 0.000 description 1
• 150000001841 cholesterols Chemical class 0.000 description 1
• 229960005025 cilazapril Drugs 0.000 description 1
• JQRZBPFGBRIWSN-YOTVLOEGSA-N cilazapril monohydrate Chemical compound O.C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 JQRZBPFGBRIWSN-YOTVLOEGSA-N 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 229910000001 cobalt(II) carbonate Inorganic materials 0.000 description 1
• 239000005516 coenzyme A Substances 0.000 description 1
• 229940093530 coenzyme a Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000002844 continuous effect Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 229950003040 dalvastatin Drugs 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 238000005695 dehalogenation reaction Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 229960005227 delapril Drugs 0.000 description 1
• WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• VXDSGTRNDFHIJB-UHFFFAOYSA-N dihydrocompactin Natural products C12C(OC(=O)C(C)CC)CCCC2C=CC(C)C1CCC1CC(O)CC(=O)O1 VXDSGTRNDFHIJB-UHFFFAOYSA-N 0.000 description 1
• 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000004609 dihydroquinazolinyl group Chemical group N1(CN=CC2=CC=CC=C12)* 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
• MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
• 239000011363 dried mixture Substances 0.000 description 1
• 235000013601 eggs Nutrition 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 239000002792 enkephalinase inhibitor Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical group C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 description 1
• 229960001208 eplerenone Drugs 0.000 description 1
• OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
• 229960004563 eprosartan Drugs 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 230000003203 everyday effect Effects 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 229960000255 exemestane Drugs 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 229960003580 felodipine Drugs 0.000 description 1
• 229960002602 fendiline Drugs 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• 239000007888 film coating Substances 0.000 description 1
• 238000009501 film coating Methods 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 1
• 229960000326 flunarizine Drugs 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 229960002490 fosinopril Drugs 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 239000000417 fungicide Substances 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 102000045360 human SDHB Human genes 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000000640 hydroxylating effect Effects 0.000 description 1
• 208000021822 hypotensive Diseases 0.000 description 1
• 230000001077 hypotensive effect Effects 0.000 description 1
• 229960001195 imidapril Drugs 0.000 description 1
• KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 1
• 229960004340 lacidipine Drugs 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229960002394 lisinopril Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• CTEDYWAWNUHMRE-UHFFFAOYSA-M magnesium;1-fluoro-4-methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=C(F)C=C1 CTEDYWAWNUHMRE-UHFFFAOYSA-M 0.000 description 1
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• 238000003328 mesylation reaction Methods 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• 229960003739 methyclothiazide Drugs 0.000 description 1
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical group COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
• UOVPHHSFTNRQHJ-UHFFFAOYSA-N methyl 3-amino-5-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 UOVPHHSFTNRQHJ-UHFFFAOYSA-N 0.000 description 1
• GMGZRXWZOZSBED-UHFFFAOYSA-N methyl 3-nitro-5-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 GMGZRXWZOZSBED-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 229950009116 mevastatin Drugs 0.000 description 1
• 229960004438 mibefradil Drugs 0.000 description 1
• 238000004452 microanalysis Methods 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229910052750 molybdenum Inorganic materials 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• TUYWTLTWNJOZNY-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C2=NNN=N2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 TUYWTLTWNJOZNY-UHFFFAOYSA-N 0.000 description 1
• POVXOWVFLAAVBH-UHFFFAOYSA-N n-formamidoformamide Chemical compound O=CNNC=O POVXOWVFLAAVBH-UHFFFAOYSA-N 0.000 description 1
• 125000003136 n-heptyl 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])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229950010800 niguldipine Drugs 0.000 description 1
• VZWXXKDFACOXNT-UHFFFAOYSA-N niludipine Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC([N+]([O-])=O)=C1 VZWXXKDFACOXNT-UHFFFAOYSA-N 0.000 description 1
• 229950000109 niludipine Drugs 0.000 description 1
• 229960005366 nilvadipine Drugs 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 229940126347 non-steroidal aldosterone synthase inhibitor Drugs 0.000 description 1
• ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
• BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• LVRLSYPNFFBYCZ-VGWMRTNUSA-N omapatrilat Chemical compound C([C@H](S)C(=O)N[C@H]1CCS[C@H]2CCC[C@H](N2C1=O)C(=O)O)C1=CC=CC=C1 LVRLSYPNFFBYCZ-VGWMRTNUSA-N 0.000 description 1
• 229950000973 omapatrilat Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 238000007833 oxidative deamination reaction Methods 0.000 description 1
• 238000005800 oxidative debenzylation reaction Methods 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 239000005022 packaging material Substances 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 229940015212 parid Drugs 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical class C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 229960002582 perindopril Drugs 0.000 description 1
• IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 1
• AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 1
• BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 235000021018 plums Nutrition 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000021395 porridge Nutrition 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 208000013846 primary aldosteronism Diseases 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011241 protective layer Substances 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 229960001455 quinapril Drugs 0.000 description 1
• JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 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
• 150000003254 radicals Chemical class 0.000 description 1
• 229910052705 radium Inorganic materials 0.000 description 1
• 229960003401 ramipril Drugs 0.000 description 1
• HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000029865 regulation of blood pressure Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229950006241 saprisartan Drugs 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000008279 sol Substances 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 229960002909 spirapril Drugs 0.000 description 1
• HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
• 108700035424 spirapril Proteins 0.000 description 1
• 229960002256 spironolactone Drugs 0.000 description 1
• LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
• SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 1
• 229950001870 spizofurone Drugs 0.000 description 1
• 230000005477 standard model Effects 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000000475 sunscreen effect Effects 0.000 description 1
• 239000000516 sunscreening agent Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229960005187 telmisartan Drugs 0.000 description 1
• 229960004084 temocapril Drugs 0.000 description 1
• FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229950000584 tezosentan Drugs 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 239000003451 thiazide diuretic agent Substances 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• AWLHTKVMDZVIGU-UHFFFAOYSA-N tin;dihydrochloride Chemical compound Cl.Cl.[Sn] AWLHTKVMDZVIGU-UHFFFAOYSA-N 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 239000003860 topical agent Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• 229960002051 trandolapril Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
• 229940117972 triolein Drugs 0.000 description 1
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1