TWI547484B - 異喹啉化合物，其製備方法及含其之醫藥組合物 - Google Patents

Info

Publication number

TWI547484B

TWI547484B TW104105729A TW104105729A TWI547484B TW I547484 B TWI547484 B TW I547484B TW 104105729 A TW104105729 A TW 104105729A TW 104105729 A TW104105729 A TW 104105729A TW I547484 B TWI547484 B TW I547484B

Authority

TW

Taiwan

Prior art keywords

nmr

group

dmso

compound

pharmaceutically acceptable

Prior art date

2014-02-21

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 51
• 238000002360 preparation method Methods 0.000 title claims description 36
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
• 230000008569 process Effects 0.000 title description 6
• 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 2
• 238000005859 coupling reaction Methods 0.000 claims description 116
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 107
• 150000001875 compounds Chemical class 0.000 claims description 97
• -1 N -cyclopentylglycine decylamine Chemical compound 0.000 claims description 72
• 230000003287 optical effect Effects 0.000 claims description 69
• 150000003839 salts Chemical class 0.000 claims description 69
• 239000002253 acid Substances 0.000 claims description 68
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 53
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 49
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 46
• 230000015572 biosynthetic process Effects 0.000 claims description 34
• 150000004677 hydrates Chemical class 0.000 claims description 34
• 239000007858 starting material Substances 0.000 claims description 29
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 25
• 150000007513 acids Chemical class 0.000 claims description 25
• 229910052799 carbon Inorganic materials 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 17
• 150000001721 carbon Chemical group 0.000 claims description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 239000003054 catalyst Substances 0.000 claims description 11
• CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 11
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 239000011435 rock Substances 0.000 claims description 9
• 230000004913 activation Effects 0.000 claims description 8
• 238000006722 reduction reaction Methods 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 208000010412 Glaucoma Diseases 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 230000026731 phosphorylation Effects 0.000 claims description 7
• 238000006366 phosphorylation reaction Methods 0.000 claims description 7
• 150000002430 hydrocarbons Chemical group 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
• TWASBYPJZBHZQJ-UHFFFAOYSA-N 1-methylcyclopentan-1-amine Chemical compound CC1(N)CCCC1 TWASBYPJZBHZQJ-UHFFFAOYSA-N 0.000 claims description 5
• 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 claims description 5
• 102000016349 Myosin Light Chains Human genes 0.000 claims description 5
• 108010067385 Myosin Light Chains Proteins 0.000 claims description 5
• 101150111584 RHOA gene Proteins 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• 208000037849 arterial hypertension Diseases 0.000 claims description 4
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 claims description 4
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 4
• 208000010125 myocardial infarction Diseases 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 239000003960 organic solvent Substances 0.000 claims description 4
• 229910052763 palladium Inorganic materials 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 230000009885 systemic effect Effects 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• DYIUGUJFYHGQBI-UHFFFAOYSA-N 1-[3,5-difluoro-4-(isoquinolin-5-ylmethyl)phenyl]ethanamine Chemical compound FC=1C=C(C=C(C=1CC1=C2C=CN=CC2=CC=C1)F)C(C)N DYIUGUJFYHGQBI-UHFFFAOYSA-N 0.000 claims description 3
• KUZXQXCWRNFIHK-UHFFFAOYSA-N 3,3-diethyldodecane Chemical compound CCCCCCCCCC(CC)(CC)CC KUZXQXCWRNFIHK-UHFFFAOYSA-N 0.000 claims description 3
• 208000031104 Arterial Occlusive disease Diseases 0.000 claims description 3
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
• 206010019280 Heart failures Diseases 0.000 claims description 3
• 206010072877 Intestinal fibrosis Diseases 0.000 claims description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 3
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 208000007474 aortic aneurysm Diseases 0.000 claims description 3
• 208000021328 arterial occlusion Diseases 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 201000001881 impotence Diseases 0.000 claims description 3
• 208000001286 intracranial vasospasm Diseases 0.000 claims description 3
• 230000003902 lesion Effects 0.000 claims description 3
• 208000019423 liver disease Diseases 0.000 claims description 3
• 230000037361 pathway Effects 0.000 claims description 3
• 230000002093 peripheral effect Effects 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 229910052707 ruthenium Inorganic materials 0.000 claims description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 208000004998 Abdominal Pain Diseases 0.000 claims description 2
• 201000006474 Brain Ischemia Diseases 0.000 claims description 2
• BLHFTQXWHLUGJE-UHFFFAOYSA-N C1CN(C2=CC(=C(C(=C21)F)C(=O)C3=CC=CC4=C3C=CNC4=O)F)N Chemical compound C1CN(C2=CC(=C(C(=C21)F)C(=O)C3=CC=CC4=C3C=CNC4=O)F)N BLHFTQXWHLUGJE-UHFFFAOYSA-N 0.000 claims description 2
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
• 208000002881 Colic Diseases 0.000 claims description 2
• PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
• 208000007536 Thrombosis Diseases 0.000 claims description 2
• JQFABIADGHVJOR-UHFFFAOYSA-N [4-(2-aminopropan-2-yl)-2,6-difluorophenyl]-isoquinolin-5-ylmethanone Chemical compound NC(C)(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=CC2=CC=C1)F JQFABIADGHVJOR-UHFFFAOYSA-N 0.000 claims description 2
• YOQPTORFJXGRNM-APDXDRDNSA-N [4-[(1S)-1-aminoethyl]-2,6-difluorophenyl]-isoquinolin-5-ylmethanol Chemical compound N[C@@H](C)C1=CC(=C(C(=C1)F)C(O)C1=C2C=CN=CC2=CC=C1)F YOQPTORFJXGRNM-APDXDRDNSA-N 0.000 claims description 2
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
• 238000002399 angioplasty Methods 0.000 claims description 2
• 206010008118 cerebral infarction Diseases 0.000 claims 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 claims description 2
• 206010061989 glomerulosclerosis Diseases 0.000 claims description 2
• 201000001421 hyperglycemia Diseases 0.000 claims description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
• 231100000252 nontoxic Toxicity 0.000 claims description 2
• 230000003000 nontoxic effect Effects 0.000 claims description 2
• IPBPLHNLRKRLPJ-UHFFFAOYSA-N oxan-4-ylmethanamine Chemical group NCC1CCOCC1 IPBPLHNLRKRLPJ-UHFFFAOYSA-N 0.000 claims description 2
• 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
• 230000002194 synthesizing effect Effects 0.000 claims 3
• AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 claims 2
• 239000005711 Benzoic acid Substances 0.000 claims 1
• 206010011026 Corneal lesion Diseases 0.000 claims 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims 1
• 206010022489 Insulin Resistance Diseases 0.000 claims 1
• 208000011623 Obstructive Lung disease Diseases 0.000 claims 1
• MZQREGYHCORZLY-UHFFFAOYSA-N [4-(1-aminoethyl)-2,6-difluorophenyl]-isoquinolin-5-ylmethanone Chemical compound NC(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=CC2=CC=C1)F MZQREGYHCORZLY-UHFFFAOYSA-N 0.000 claims 1
• 229910021538 borax Inorganic materials 0.000 claims 1
• UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 239000000835 fiber Substances 0.000 claims 1
• 230000004761 fibrosis Effects 0.000 claims 1
• 239000004328 sodium tetraborate Substances 0.000 claims 1
• 235000010339 sodium tetraborate Nutrition 0.000 claims 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
• 239000000543 intermediate Substances 0.000 description 1119
• 238000005481 NMR spectroscopy Methods 0.000 description 427
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 176
• 239000000203 mixture Substances 0.000 description 156
• 239000000243 solution Substances 0.000 description 156
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
• 230000008878 coupling Effects 0.000 description 105
• 238000010168 coupling process Methods 0.000 description 105
• 230000001590 oxidative effect Effects 0.000 description 99
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 98
• 239000007787 solid Substances 0.000 description 88
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
• 239000012074 organic phase Substances 0.000 description 85
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
• 239000011541 reaction mixture Substances 0.000 description 79
• 239000000460 chlorine Substances 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 55
• 235000019439 ethyl acetate Nutrition 0.000 description 55
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
• 239000000047 product Substances 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 45
• 239000002904 solvent Substances 0.000 description 45
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 38
• 229920006395 saturated elastomer Polymers 0.000 description 37
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 31
• 238000001514 detection method Methods 0.000 description 31
• 239000003921 oil Substances 0.000 description 30
• 235000019198 oils Nutrition 0.000 description 30
• 230000002829 reductive effect Effects 0.000 description 28
• 238000004587 chromatography analysis Methods 0.000 description 26
• 238000003786 synthesis reaction Methods 0.000 description 25
• 239000000706 filtrate Substances 0.000 description 24
• 239000011780 sodium chloride Substances 0.000 description 23
• 239000003480 eluent Substances 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 21
• 229910002027 silica gel Inorganic materials 0.000 description 21
• 150000001412 amines Chemical class 0.000 description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 238000001704 evaporation Methods 0.000 description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
• CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 17
• 230000008020 evaporation Effects 0.000 description 17
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 150000002576 ketones Chemical class 0.000 description 16
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
• 239000002244 precipitate Substances 0.000 description 15
• 239000008346 aqueous phase Substances 0.000 description 14
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 14
• 238000012544 monitoring process Methods 0.000 description 14
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 13
• 238000004128 high performance liquid chromatography Methods 0.000 description 13
• 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 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
• 239000000377 silicon dioxide Substances 0.000 description 12
• 229910000420 cerium oxide Inorganic materials 0.000 description 11
• 239000012467 final product Substances 0.000 description 11
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 11
• 238000004808 supercritical fluid chromatography Methods 0.000 description 11
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• 230000002378 acidificating effect Effects 0.000 description 10
• CETPSERCERDGAM-UHFFFAOYSA-N ceric oxide Chemical compound O=[Ce]=O CETPSERCERDGAM-UHFFFAOYSA-N 0.000 description 10
• 229910000422 cerium(IV) oxide Inorganic materials 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• CESUXLKAADQNTB-ZETCQYMHSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](N)=O CESUXLKAADQNTB-ZETCQYMHSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 239000007864 aqueous solution Substances 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 7
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 7
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
• 108010041788 rho-Associated Kinases Proteins 0.000 description 7
• 102000000568 rho-Associated Kinases Human genes 0.000 description 7
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 7
• 235000012239 silicon dioxide Nutrition 0.000 description 7
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 206010028980 Neoplasm Diseases 0.000 description 6
• 230000004872 arterial blood pressure Effects 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 6
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 6
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
• 229910052786 argon Inorganic materials 0.000 description 5
• 230000008602 contraction Effects 0.000 description 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 5
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 4
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 4
• HBVVKRYLYPANAE-UHFFFAOYSA-N 4,6-difluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC(F)=CC2=C1CCC2=O HBVVKRYLYPANAE-UHFFFAOYSA-N 0.000 description 4
• SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 4
• 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 230000031709 bromination Effects 0.000 description 4
• 238000005893 bromination reaction Methods 0.000 description 4
• 230000004663 cell proliferation Effects 0.000 description 4
• GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 230000001965 increasing effect Effects 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 239000007937 lozenge Substances 0.000 description 4
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
• 238000013508 migration Methods 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 239000002504 physiological saline solution Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 238000011084 recovery Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 239000003590 rho kinase inhibitor Substances 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 238000011699 spontaneously hypertensive rat Methods 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 238000012360 testing method Methods 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
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 4
• 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 4
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 3
• OXJLDNSPGPBDCP-UHFFFAOYSA-N 1-(3,5-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC(F)=C1 OXJLDNSPGPBDCP-UHFFFAOYSA-N 0.000 description 3
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 3
• YCCQGFYAVUTQFK-UHFFFAOYSA-N 2,3-difluoroaniline Chemical compound NC1=CC=CC(F)=C1F YCCQGFYAVUTQFK-UHFFFAOYSA-N 0.000 description 3
• MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• GONAVIHGXFBTOZ-UHFFFAOYSA-N 3,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(F)=C1 GONAVIHGXFBTOZ-UHFFFAOYSA-N 0.000 description 3
• SLDLVGFPFFLYBM-UHFFFAOYSA-N 3-fluoro-2-methyl-aniline Chemical compound CC1=C(N)C=CC=C1F SLDLVGFPFFLYBM-UHFFFAOYSA-N 0.000 description 3
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
• ITPYJIMXMPQSBK-UHFFFAOYSA-N 4-bromo-2,3-difluorobenzonitrile Chemical compound FC1=C(F)C(C#N)=CC=C1Br ITPYJIMXMPQSBK-UHFFFAOYSA-N 0.000 description 3
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• JRGKLCLDTYLMAS-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)F JRGKLCLDTYLMAS-UHFFFAOYSA-N 0.000 description 3
• 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 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 101150003085 Pdcl gene Proteins 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 3
• 229940043377 alpha-cyclodextrin Drugs 0.000 description 3
• 229960004050 aminobenzoic acid Drugs 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• PKSBCKIJVULJIF-UHFFFAOYSA-N butane-1-sulfinamide Chemical compound CCCCS(N)=O PKSBCKIJVULJIF-UHFFFAOYSA-N 0.000 description 3
• SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical compound CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 3
• 238000005251 capillar electrophoresis Methods 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 210000004027 cell Anatomy 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000010908 decantation Methods 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 210000003038 endothelium Anatomy 0.000 description 3
• 230000002255 enzymatic effect Effects 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000013067 intermediate product Substances 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 229940098779 methanesulfonic acid Drugs 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 150000002923 oximes Chemical class 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 239000010948 rhodium Substances 0.000 description 3
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• CJWGCBRQAHCVHW-ZETCQYMHSA-N (1s)-1-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC([C@H](C)N)=C1 CJWGCBRQAHCVHW-ZETCQYMHSA-N 0.000 description 2
• SOZMSEPDYJGBEK-LURJTMIESA-N (1s)-1-(4-bromophenyl)ethanamine Chemical compound C[C@H](N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-LURJTMIESA-N 0.000 description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
• QEWHNJPLPZOEKU-UHFFFAOYSA-N 1-(2,4-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1F QEWHNJPLPZOEKU-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• JKRDHBJTRKCBHS-UHFFFAOYSA-N 1-[4-(1-ethoxy-3-methylisoquinoline-5-carbonyl)-3,5-difluoro-2-methoxyphenyl]ethylcarbamic acid Chemical compound CCOc1nc(C)cc2c(cccc12)C(=O)c1c(F)cc(C(C)NC(O)=O)c(OC)c1F JKRDHBJTRKCBHS-UHFFFAOYSA-N 0.000 description 2
• LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 2
• 238000004293 19F NMR spectroscopy Methods 0.000 description 2
• HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
• WCGPCBACLBHDCI-UHFFFAOYSA-N 2,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1 WCGPCBACLBHDCI-UHFFFAOYSA-N 0.000 description 2
• IWPZKOJSYQZABD-UHFFFAOYSA-N 3,5-dimethoxybenzoic acid Chemical compound COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 description 2
• OUAZPCKRSSEQKB-UHFFFAOYSA-N 3-bromo-2-fluorobenzaldehyde Chemical compound FC1=C(Br)C=CC=C1C=O OUAZPCKRSSEQKB-UHFFFAOYSA-N 0.000 description 2
• UPCARQPLANFGQJ-UHFFFAOYSA-N 4-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC(Br)=CC=C1C=O UPCARQPLANFGQJ-UHFFFAOYSA-N 0.000 description 2
• LRMUGJVHRUVMHP-UHFFFAOYSA-N 4-bromo-3,5-difluorobenzonitrile Chemical compound FC1=CC(C#N)=CC(F)=C1Br LRMUGJVHRUVMHP-UHFFFAOYSA-N 0.000 description 2
• WTNCRDVVJCQOOF-UHFFFAOYSA-N 4-bromo-3-fluoro-5-methylaniline Chemical compound CC1=CC(N)=CC(F)=C1Br WTNCRDVVJCQOOF-UHFFFAOYSA-N 0.000 description 2
• XWZGNWCKXLECBO-UHFFFAOYSA-N 5,7-difluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC(F)=CC2=C1C(=O)CC2 XWZGNWCKXLECBO-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 102000007469 Actins Human genes 0.000 description 2
• 108010085238 Actins Proteins 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• PBDWDGYUTHUOSH-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1F)C1N(CCC1)C(=O)OC(C)(C)C)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1F)C1N(CCC1)C(=O)OC(C)(C)C)F PBDWDGYUTHUOSH-UHFFFAOYSA-N 0.000 description 2
• CHFCTLXKNBROGI-UHFFFAOYSA-N CC(C1=CC=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)NNC(=O)OC(C)(C)C Chemical compound CC(C1=CC=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)NNC(=O)OC(C)(C)C CHFCTLXKNBROGI-UHFFFAOYSA-N 0.000 description 2
• GPNZGYLDQQARRN-UHFFFAOYSA-N CC1=CC2=C(CCN2NC(=O)OC(C)(C)C)C=C1C(=O)C3=CC=CC4=C3C=CN=C4 Chemical compound CC1=CC2=C(CCN2NC(=O)OC(C)(C)C)C=C1C(=O)C3=CC=CC4=C3C=CN=C4 GPNZGYLDQQARRN-UHFFFAOYSA-N 0.000 description 2
• CIQAMGJBDGEPID-UHFFFAOYSA-N CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C4C(=C3F)CCN4N)F Chemical compound CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C4C(=C3F)CCN4N)F CIQAMGJBDGEPID-UHFFFAOYSA-N 0.000 description 2
• HNZOFGMODLLZFQ-UHFFFAOYSA-N CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C4C(=C3F)CCN4NC(=O)OC(C)(C)C)F Chemical compound CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C4C(=C3F)CCN4NC(=O)OC(C)(C)C)F HNZOFGMODLLZFQ-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 2
• 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 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000872931 Myoporum sandwicense Species 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• OKLUZMUKXYWEGD-UHFFFAOYSA-N N-bromobutan-1-imine Chemical compound CCCC=NBr OKLUZMUKXYWEGD-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-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
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 2
• 229910004298 SiO 2 Inorganic materials 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 210000002376 aorta thoracic Anatomy 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 230000009787 cardiac fibrosis Effects 0.000 description 2
• 230000012292 cell migration Effects 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000007336 electrophilic substitution reaction Methods 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 2
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 238000002329 infrared spectrum Methods 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• HSPKIXPRSRGOQK-UHFFFAOYSA-N isoquinolin-5-ylmethanol Chemical compound N1=CC=C2C(CO)=CC=CC2=C1 HSPKIXPRSRGOQK-UHFFFAOYSA-N 0.000 description 2
• 150000002537 isoquinolines Chemical class 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 229940091250 magnesium supplement Drugs 0.000 description 2
• IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 150000004702 methyl esters Chemical group 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 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 2
• XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
• 230000001537 neural effect Effects 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 229960003975 potassium Drugs 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 201000002793 renal fibrosis Diseases 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-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
• 239000011877 solvent mixture Substances 0.000 description 2
• HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 2
• CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 2
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
• BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• CJWGCBRQAHCVHW-SSDOTTSWSA-N (1r)-1-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC([C@@H](C)N)=C1 CJWGCBRQAHCVHW-SSDOTTSWSA-N 0.000 description 1
• FUTIQTRSQNCRKC-UHFFFAOYSA-N (2,6-difluoro-4-piperidin-2-ylphenyl)-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound FC1=C(C(=CC(=C1)C1NCCCC1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC FUTIQTRSQNCRKC-UHFFFAOYSA-N 0.000 description 1
• QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 1
• CTVUGTISPMOHSP-UHFFFAOYSA-N (4-bromo-2,5-difluorophenyl)-isoquinolin-5-ylmethanone Chemical compound BrC1=CC(=C(C=C1F)C(=O)C1=C2C=CN=CC2=CC=C1)F CTVUGTISPMOHSP-UHFFFAOYSA-N 0.000 description 1
• OXJOPYYPGHMMFB-UHFFFAOYSA-N (4-bromo-2,6-difluorophenyl)-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound BrC1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F OXJOPYYPGHMMFB-UHFFFAOYSA-N 0.000 description 1
• UESGUDNCVMBHSQ-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound BrC1=CC(=C(C=C1)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F UESGUDNCVMBHSQ-UHFFFAOYSA-N 0.000 description 1
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
• FZENGILVLUJGJX-IHWYPQMZSA-N (Z)-acetaldehyde oxime Chemical compound C\C=N/O FZENGILVLUJGJX-IHWYPQMZSA-N 0.000 description 1
• UJPMYEOUBPIPHQ-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound CC(F)(F)F UJPMYEOUBPIPHQ-UHFFFAOYSA-N 0.000 description 1
• OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
• DKYBVKMIZODYKL-UHFFFAOYSA-N 1,3-diazinane Chemical compound C1CNCNC1 DKYBVKMIZODYKL-UHFFFAOYSA-N 0.000 description 1
• VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
• KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
• GLVMLJCMUBZVTJ-UHFFFAOYSA-N 1,4-dibromo-2,5-difluorobenzene Chemical compound FC1=CC(Br)=C(F)C=C1Br GLVMLJCMUBZVTJ-UHFFFAOYSA-N 0.000 description 1
• PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 1
• BKIHFZLJJUNKMZ-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC(C)=CC(C)=C1 BKIHFZLJJUNKMZ-UHFFFAOYSA-N 0.000 description 1
• SOZMSEPDYJGBEK-UHFFFAOYSA-N 1-(4-bromophenyl)ethanamine Chemical compound CC(N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-UHFFFAOYSA-N 0.000 description 1
• BIXHDNKYJLVBCQ-UHFFFAOYSA-N 1-[3-(1-ethoxyisoquinoline-5-carbonyl)-2,4-difluoro-6-phenylmethoxyphenyl]ethylcarbamic acid Chemical compound CCOc1nccc2c(cccc12)C(=O)c1c(F)cc(OCc2ccccc2)c(C(C)NC(O)=O)c1F BIXHDNKYJLVBCQ-UHFFFAOYSA-N 0.000 description 1
• FRCRTGOAVZHTIR-UHFFFAOYSA-N 1-[4-(1-ethoxyisoquinoline-5-carbonyl)-3,5-difluoro-2-phenylmethoxyphenyl]ethylcarbamic acid Chemical compound CCOc1nccc2c(cccc12)C(=O)c1c(F)cc(C(C)NC(O)=O)c(OCc2ccccc2)c1F FRCRTGOAVZHTIR-UHFFFAOYSA-N 0.000 description 1
• FIFUXPUZXQBMHT-UHFFFAOYSA-N 1-[4-(1-ethoxyisoquinoline-5-carbonyl)-3-fluoro-2-(2-methylpropoxy)phenyl]ethylcarbamic acid Chemical compound CCOc1nccc2c(cccc12)C(=O)c1ccc(C(C)NC(O)=O)c(OCC(C)C)c1F FIFUXPUZXQBMHT-UHFFFAOYSA-N 0.000 description 1
• FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 1
• MLIFKSSUZINVQO-UHFFFAOYSA-N 1-bromo-2-fluoro-4-iodo-3-methylbenzene Chemical compound CC1=C(F)C(Br)=CC=C1I MLIFKSSUZINVQO-UHFFFAOYSA-N 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• JHLKSIOJYMGSMB-UHFFFAOYSA-N 1-bromo-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(Br)=C1 JHLKSIOJYMGSMB-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
• GYZUAQKYFPQTAP-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[3-fluoro-4-(isoquinolin-5-ylmethyl)phenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C=C1)CC1=C2C=CN=CC2=CC=C1)F)(F)F GYZUAQKYFPQTAP-UHFFFAOYSA-N 0.000 description 1
• DUDKGOYNSIANAK-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[3-fluoro-4-(isoquinoline-5-carbonyl)-5-methoxyphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)OC)C(=O)C1=C2C=CN=CC2=CC=C1)F)(F)F DUDKGOYNSIANAK-UHFFFAOYSA-N 0.000 description 1
• DYEKUQKJZRKGMB-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[3-fluoro-4-[hydroxy(isoquinolin-5-yl)methyl]-5-methoxyphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)OC)C(C1=C2C=CN=CC2=CC=C1)O)F)(F)F DYEKUQKJZRKGMB-UHFFFAOYSA-N 0.000 description 1
• SMLHYILUQRYWOG-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[3-hydroxy-4-(isoquinoline-5-carbonyl)-5-methoxyphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)OC)C(=O)C1=C2C=CN=CC2=CC=C1)O)(F)F SMLHYILUQRYWOG-UHFFFAOYSA-N 0.000 description 1
• DSUPBROQSKPAAX-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[3-hydroxy-4-(isoquinoline-5-carbonyl)-5-methylphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)C)C(=O)C1=C2C=CN=CC2=CC=C1)O)(F)F DSUPBROQSKPAAX-UHFFFAOYSA-N 0.000 description 1
• DOPCAHVXXHUXCD-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[4-(isoquinoline-5-carbonyl)-3,5-dimethoxyphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)OC)C(=O)C1=C2C=CN=CC2=CC=C1)OC)(F)F DOPCAHVXXHUXCD-UHFFFAOYSA-N 0.000 description 1
• ZORWUAONIKWEOY-UHFFFAOYSA-N 2,2,2-trifluoro-N-[1-[4-(isoquinoline-5-carbonyl)-3-methoxy-5-methylphenyl]ethyl]acetamide Chemical compound FC(C(=O)NC(C)C1=CC(=C(C(=C1)C)C(=O)C1=C2C=CN=CC2=CC=C1)OC)(F)F ZORWUAONIKWEOY-UHFFFAOYSA-N 0.000 description 1
• IANXAXNUNBAWBA-UHFFFAOYSA-N 2,2,3-trimethylundecane Chemical compound CCCCCCCCC(C)C(C)(C)C IANXAXNUNBAWBA-UHFFFAOYSA-N 0.000 description 1
• VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical compound CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 description 1
• LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
• NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
• YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 description 1
• WOLGNRYEQPISPB-UHFFFAOYSA-N 2-bromo-1,3-difluoro-5-iodobenzene Chemical compound FC1=CC(I)=CC(F)=C1Br WOLGNRYEQPISPB-UHFFFAOYSA-N 0.000 description 1
• GEJMNTXYFBBTFH-UHFFFAOYSA-N 2-bromo-1,3-difluoro-5-methoxybenzene Chemical compound COC1=CC(F)=C(Br)C(F)=C1 GEJMNTXYFBBTFH-UHFFFAOYSA-N 0.000 description 1
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
• KWMBADTWRIGGGG-UHFFFAOYSA-N 2-diethoxyphosphorylacetonitrile Chemical compound CCOP(=O)(CC#N)OCC KWMBADTWRIGGGG-UHFFFAOYSA-N 0.000 description 1
• FVTWJXMFYOXOKK-UHFFFAOYSA-N 2-fluoroacetamide Chemical compound NC(=O)CF FVTWJXMFYOXOKK-UHFFFAOYSA-N 0.000 description 1
• HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• KQOIBXZRCYFZSO-UHFFFAOYSA-N 3,5-difluoroaniline Chemical compound NC1=CC(F)=CC(F)=C1 KQOIBXZRCYFZSO-UHFFFAOYSA-N 0.000 description 1
• ASOFZHSTJHGQDT-UHFFFAOYSA-N 3,5-difluorobenzaldehyde Chemical compound FC1=CC(F)=CC(C=O)=C1 ASOFZHSTJHGQDT-UHFFFAOYSA-N 0.000 description 1
• CQXZSEXZQVKCHW-UHFFFAOYSA-N 3,5-difluorobenzonitrile Chemical compound FC1=CC(F)=CC(C#N)=C1 CQXZSEXZQVKCHW-UHFFFAOYSA-N 0.000 description 1
• HJSSBIMVTMYKPD-UHFFFAOYSA-N 3,5-difluorophenol Chemical compound OC1=CC(F)=CC(F)=C1 HJSSBIMVTMYKPD-UHFFFAOYSA-N 0.000 description 1
• HQLLUIGQAYVFBX-UHFFFAOYSA-N 3-(3-bromo-4-methoxyphenyl)propanenitrile Chemical compound COC1=CC=C(CCC#N)C=C1Br HQLLUIGQAYVFBX-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
• WPDXAMRGYMDTOV-UHFFFAOYSA-N 3-bromo-2-methylphenol Chemical compound CC1=C(O)C=CC=C1Br WPDXAMRGYMDTOV-UHFFFAOYSA-N 0.000 description 1
• QWTULQLVGNZMLF-UHFFFAOYSA-N 3-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C(Br)=C1 QWTULQLVGNZMLF-UHFFFAOYSA-N 0.000 description 1
• WTXXUAHMTVAQHW-UHFFFAOYSA-N 3-bromo-4-methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C=C1Br WTXXUAHMTVAQHW-UHFFFAOYSA-N 0.000 description 1
• LPIFAHAICWJMRR-UHFFFAOYSA-N 3-chloro-5-fluoroaniline Chemical compound NC1=CC(F)=CC(Cl)=C1 LPIFAHAICWJMRR-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
• BHWSRJOKTBUWBN-UHFFFAOYSA-N 3-fluoro-5-methoxyaniline Chemical compound COC1=CC(N)=CC(F)=C1 BHWSRJOKTBUWBN-UHFFFAOYSA-N 0.000 description 1
• DPHBKGYVIHTBDG-UHFFFAOYSA-N 3-fluoro-5-methylaniline Chemical compound CC1=CC(N)=CC(F)=C1 DPHBKGYVIHTBDG-UHFFFAOYSA-N 0.000 description 1
• ALUKWQVSCATDLJ-UHFFFAOYSA-N 3-methoxy-5-methylbenzoic acid Chemical compound COC1=CC(C)=CC(C(O)=O)=C1 ALUKWQVSCATDLJ-UHFFFAOYSA-N 0.000 description 1
• KCHQXPGUJBVNTN-UHFFFAOYSA-N 4,4-diphenylbut-3-en-2-one Chemical compound C=1C=CC=CC=1C(=CC(=O)C)C1=CC=CC=C1 KCHQXPGUJBVNTN-UHFFFAOYSA-N 0.000 description 1
• VPWCHSYGVODOFZ-UHFFFAOYSA-N 4-(1-ethoxyisoquinoline-5-carbonyl)-3-fluorobenzonitrile Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C#N)C=C1)F VPWCHSYGVODOFZ-UHFFFAOYSA-N 0.000 description 1
• OVCQAKMWJUQECU-UHFFFAOYSA-N 4-bromo-2-ethoxy-3-fluorobenzonitrile Chemical compound BrC1=C(C(=C(C#N)C=C1)OCC)F OVCQAKMWJUQECU-UHFFFAOYSA-N 0.000 description 1
• VOPLRYDSRVEQDI-UHFFFAOYSA-N 4-bromo-3-chloro-5-fluoroaniline Chemical compound NC1=CC(F)=C(Br)C(Cl)=C1 VOPLRYDSRVEQDI-UHFFFAOYSA-N 0.000 description 1
• QLYHPNUFNZJXOQ-UHFFFAOYSA-N 4-bromo-3-chloroaniline Chemical compound NC1=CC=C(Br)C(Cl)=C1 QLYHPNUFNZJXOQ-UHFFFAOYSA-N 0.000 description 1
• PSKJIHDVFDVNBU-UHFFFAOYSA-N 4-bromo-3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(Cl)=C1 PSKJIHDVFDVNBU-UHFFFAOYSA-N 0.000 description 1
• LQDRJGHJODSHJO-UHFFFAOYSA-N 4-bromo-3-fluoro-2-(2-methylpropoxy)benzonitrile Chemical compound BrC1=C(C(=C(C#N)C=C1)OCC(C)C)F LQDRJGHJODSHJO-UHFFFAOYSA-N 0.000 description 1
• LNVJWSAJCOUHDU-UHFFFAOYSA-N 4-bromo-3-fluoro-5-methoxyaniline Chemical compound COC1=CC(N)=CC(F)=C1Br LNVJWSAJCOUHDU-UHFFFAOYSA-N 0.000 description 1
• RMYOGXPGIDWJLU-UHFFFAOYSA-N 4-bromo-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(F)=C1 RMYOGXPGIDWJLU-UHFFFAOYSA-N 0.000 description 1
• RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 1
• SKXUZFJOLNNWIG-UHFFFAOYSA-N 4-bromo-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1Br SKXUZFJOLNNWIG-UHFFFAOYSA-N 0.000 description 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
• XTUSSUGGUMAIJG-UHFFFAOYSA-N 5-[(2,6-difluoro-4-methoxyphenyl)methyl]isoquinoline Chemical compound FC1=C(CC2=C3C=CN=CC3=CC=C2)C(=CC(=C1)OC)F XTUSSUGGUMAIJG-UHFFFAOYSA-N 0.000 description 1
• XWWKNWMRKOKNJE-UHFFFAOYSA-N 5-[4-(1-aminoethyl)-2,6-difluorobenzoyl]-2H-isoquinolin-1-one hydrochloride Chemical compound Cl.CC(N)c1cc(F)c(C(=O)c2cccc3c2cc[nH]c3=O)c(F)c1 XWWKNWMRKOKNJE-UHFFFAOYSA-N 0.000 description 1
• KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 1
• UOPZFPWKIZTDRV-UHFFFAOYSA-N 5-bromo-6-methoxy-2,3-dihydroinden-1-one Chemical compound C1=C(Br)C(OC)=CC2=C1CCC2=O UOPZFPWKIZTDRV-UHFFFAOYSA-N 0.000 description 1
• ZUGAOYSWHHGDJY-UHFFFAOYSA-K 5-hydroxy-2,8,9-trioxa-1-aluminabicyclo[3.3.2]decane-3,7,10-trione Chemical compound [Al+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZUGAOYSWHHGDJY-UHFFFAOYSA-K 0.000 description 1
• WSXOURRQDMFDRD-UHFFFAOYSA-N 5-methyl-2h-isoquinolin-1-one Chemical compound N1=CC=C2C(C)=CC=CC2=C1O WSXOURRQDMFDRD-UHFFFAOYSA-N 0.000 description 1
• BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
• 102100023818 ADP-ribosylation factor 3 Human genes 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 241000349731 Afzelia bipindensis Species 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 102000005862 Angiotensin II Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• 241000208340 Araliaceae Species 0.000 description 1
• 206010003225 Arteriospasm coronary Diseases 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 208000006386 Bone Resorption Diseases 0.000 description 1
• BJJLVLUFQGDGQT-ZETCQYMHSA-N BrC1=C(C=C(C=C1F)[C@H](C)NC(OC(C)(C)C)=O)F Chemical compound BrC1=C(C=C(C=C1F)[C@H](C)NC(OC(C)(C)C)=O)F BJJLVLUFQGDGQT-ZETCQYMHSA-N 0.000 description 1
• XHXPISSACWVBQH-UHFFFAOYSA-N BrC1=CN=C(C2=CC=CC(=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)OCC Chemical compound BrC1=CN=C(C2=CC=CC(=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)OCC XHXPISSACWVBQH-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 206010006440 Bronchial obstruction Diseases 0.000 description 1
• 208000027775 Bronchopulmonary disease Diseases 0.000 description 1
• JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
• PWRBRALVVXNTEO-UHFFFAOYSA-N C(=C)C1=C(C=C(C(=C1F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)C(C)NC(OC(C)(C)C)=O Chemical compound C(=C)C1=C(C=C(C(=C1F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)C(C)NC(OC(C)(C)C)=O PWRBRALVVXNTEO-UHFFFAOYSA-N 0.000 description 1
• HYQDYNJAEMLKMK-UHFFFAOYSA-N C(C)OC1=NC(=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F)C Chemical compound C(C)OC1=NC(=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F)C HYQDYNJAEMLKMK-UHFFFAOYSA-N 0.000 description 1
• IFMYDIYYWPTDBR-UHFFFAOYSA-N C(C)OC1=NC(=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)C Chemical compound C(C)OC1=NC(=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)C IFMYDIYYWPTDBR-UHFFFAOYSA-N 0.000 description 1
• CWNJIQDJAFPQAX-SFHVURJKSA-N C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1)[C@H](C)NC(OC(C)(C)C)=O)C)C Chemical compound C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1)[C@H](C)NC(OC(C)(C)C)=O)C)C CWNJIQDJAFPQAX-SFHVURJKSA-N 0.000 description 1
• FIPIKCDNFYROGO-UHFFFAOYSA-N C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F)C Chemical compound C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F)C FIPIKCDNFYROGO-UHFFFAOYSA-N 0.000 description 1
• GHLUZFNQFSIIAR-UHFFFAOYSA-N C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)CC Chemical compound C(C)OC1=NC=C(C2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)CC GHLUZFNQFSIIAR-UHFFFAOYSA-N 0.000 description 1
• HHJHNZBZLYEBOO-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)C)C Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)C)C HHJHNZBZLYEBOO-UHFFFAOYSA-N 0.000 description 1
• JOUSAXGHOQSQIP-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)C)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)C)F JOUSAXGHOQSQIP-UHFFFAOYSA-N 0.000 description 1
• VIANVRTWOXRSFQ-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)F)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)F)F VIANVRTWOXRSFQ-UHFFFAOYSA-N 0.000 description 1
• GATSNDIJVZFFLD-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)F)OC Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)F)OC GATSNDIJVZFFLD-UHFFFAOYSA-N 0.000 description 1
• FBDPWSRLKJDBLP-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)C Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)C FBDPWSRLKJDBLP-UHFFFAOYSA-N 0.000 description 1
• JOUSAXGHOQSQIP-INIZCTEOSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)[C@H](C)NC(OC(C)(C)C)=O)C)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1)[C@H](C)NC(OC(C)(C)C)=O)C)F JOUSAXGHOQSQIP-INIZCTEOSA-N 0.000 description 1
• NMQDQHXMHRUTSD-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)C)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)C)F NMQDQHXMHRUTSD-UHFFFAOYSA-N 0.000 description 1
• DTEFXVJFUQGIOK-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)CC)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)CC)F DTEFXVJFUQGIOK-UHFFFAOYSA-N 0.000 description 1
• NSSBMWWMNSPXGM-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)O)F NSSBMWWMNSPXGM-UHFFFAOYSA-N 0.000 description 1
• RVPHLGDJKUVSRN-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)OC)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C(=C(C=C1F)C(C)NC(OC(C)(C)C)=O)OC)F RVPHLGDJKUVSRN-UHFFFAOYSA-N 0.000 description 1
• HHQSZDYRWQVCFA-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1)C(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1)C(C)NC(OC(C)(C)C)=O)F HHQSZDYRWQVCFA-UHFFFAOYSA-N 0.000 description 1
• YXXKFXISKKOJKD-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F YXXKFXISKKOJKD-UHFFFAOYSA-N 0.000 description 1
• HJOHLPUNPUFFGJ-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F HJOHLPUNPUFFGJ-UHFFFAOYSA-N 0.000 description 1
• AXZZYOJPKPVZSU-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(CCC)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)C(CCC)NC(OC(C)(C)C)=O)F AXZZYOJPKPVZSU-UHFFFAOYSA-N 0.000 description 1
• HJOHLPUNPUFFGJ-AWEZNQCLSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)[C@H](C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(C=C1F)[C@H](C)NC(OC(C)(C)C)=O)F HJOHLPUNPUFFGJ-AWEZNQCLSA-N 0.000 description 1
• UGLUDFUERFCADL-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(CNC(OC(C)(C)C)=O)C=C1)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C1=C(C=C(CNC(OC(C)(C)C)=O)C=C1)F UGLUDFUERFCADL-UHFFFAOYSA-N 0.000 description 1
• RBEJYUMRXCSYBJ-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C(=CC=1F)C)C(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C(=CC=1F)C)C(C)NC(OC(C)(C)C)=O)F RBEJYUMRXCSYBJ-UHFFFAOYSA-N 0.000 description 1
• POCZDVCFGYINLT-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C(=CC=1F)OC)C(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C(=CC=1F)OC)C(C)NC(OC(C)(C)C)=O)F POCZDVCFGYINLT-UHFFFAOYSA-N 0.000 description 1
• WYTNPBXKFQZFQD-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1)C(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1)C(C)NC(OC(C)(C)C)=O)F WYTNPBXKFQZFQD-UHFFFAOYSA-N 0.000 description 1
• RCAVOTQEQLDHTN-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1F)C(C)(C)NC(OC(C)(C)C)=O)F Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1F)C(C)(C)NC(OC(C)(C)C)=O)F RCAVOTQEQLDHTN-UHFFFAOYSA-N 0.000 description 1
• XDADVPSOVXOCMQ-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)C)O Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(C1=C(C(=C(C=C1)C(C)NC(OC(C)(C)C)=O)OC)C)O XDADVPSOVXOCMQ-UHFFFAOYSA-N 0.000 description 1
• LVVJTUBFGCUZBI-UHFFFAOYSA-N C(C)OC1=NC=CC2=C(C=CC=C12)C(C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)O Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)O LVVJTUBFGCUZBI-UHFFFAOYSA-N 0.000 description 1
• ASACYBSHWCZTSL-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=C(C=C(C(=C1)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)C(C)NC(OC(C)(C)C)=O Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C(=C1)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)C(C)NC(OC(C)(C)C)=O ASACYBSHWCZTSL-UHFFFAOYSA-N 0.000 description 1
• ORDBYTKPRWTANV-UHFFFAOYSA-N C1(CCCCC1)CC(C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)NC(OC(C)(C)C)=O Chemical compound C1(CCCCC1)CC(C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F)NC(OC(C)(C)C)=O ORDBYTKPRWTANV-UHFFFAOYSA-N 0.000 description 1
• UKBJVDFHCHGVRH-UHFFFAOYSA-N C1(CCCCC1)CN(C(OC(C)(C)C)=O)C(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F Chemical compound C1(CCCCC1)CN(C(OC(C)(C)C)=O)C(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F UKBJVDFHCHGVRH-UHFFFAOYSA-N 0.000 description 1
• JDTZVCOPVRVVKD-UHFFFAOYSA-N C1=NC=CC2=C(C=CC=C12)C(=O)C1=CC=C(C2=C1OCCO2)C(C)NC(OC(C)(C)C)=O Chemical compound C1=NC=CC2=C(C=CC=C12)C(=O)C1=CC=C(C2=C1OCCO2)C(C)NC(OC(C)(C)C)=O JDTZVCOPVRVVKD-UHFFFAOYSA-N 0.000 description 1
• TWVGLOOEAAQPKW-UHFFFAOYSA-N C1=NC=CC2=C(C=CC=C12)C(=O)C1=CC=C(C=C1)C(C)(C)NC(OC(C)(C)C)=O Chemical compound C1=NC=CC2=C(C=CC=C12)C(=O)C1=CC=C(C=C1)C(C)(C)NC(OC(C)(C)C)=O TWVGLOOEAAQPKW-UHFFFAOYSA-N 0.000 description 1
• OESALBAGUMZDCW-UHFFFAOYSA-N CC(C)(C)N(C(=O)O)C1(CCC1)C2=CC=C(C=C2)C(=O)C3=CC=CC4=C3C=CN=C4 Chemical compound CC(C)(C)N(C(=O)O)C1(CCC1)C2=CC=C(C=C2)C(=O)C3=CC=CC4=C3C=CN=C4 OESALBAGUMZDCW-UHFFFAOYSA-N 0.000 description 1
• UDZGRYPTPBIING-UHFFFAOYSA-N CC(C)(C)OC(=O)NN1CCC2=CC(=C(C=C21)OC)C(=O)C3=CC=CC4=C3C=CN=C4 Chemical compound CC(C)(C)OC(=O)NN1CCC2=CC(=C(C=C21)OC)C(=O)C3=CC=CC4=C3C=CN=C4 UDZGRYPTPBIING-UHFFFAOYSA-N 0.000 description 1
• RNPRXNVYZPLQMZ-UHFFFAOYSA-N CC(C1=CC(=C(C(=C1)F)C(=O)C2=CC=CC3=C2C=CN=C3)F)NNC(=O)OC(C)(C)C Chemical compound CC(C1=CC(=C(C(=C1)F)C(=O)C2=CC=CC3=C2C=CN=C3)F)NNC(=O)OC(C)(C)C RNPRXNVYZPLQMZ-UHFFFAOYSA-N 0.000 description 1
• MYMKYWSKGRMVBJ-UHFFFAOYSA-N CC(C1=CC(=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)O)NNC(=O)OC(C)(C)C Chemical compound CC(C1=CC(=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)O)NNC(=O)OC(C)(C)C MYMKYWSKGRMVBJ-UHFFFAOYSA-N 0.000 description 1
• PFSPLKUXUUBBGJ-UHFFFAOYSA-N CC(C1=CC(=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)OC)NNC(=O)OC(C)(C)C Chemical compound CC(C1=CC(=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)OC)NNC(=O)OC(C)(C)C PFSPLKUXUUBBGJ-UHFFFAOYSA-N 0.000 description 1
• UDODQZLHXZBDJC-UHFFFAOYSA-N CC(CCCCCCCCCC#N)(C)C Chemical compound CC(CCCCCCCCCC#N)(C)C UDODQZLHXZBDJC-UHFFFAOYSA-N 0.000 description 1
• PACIBGNGCBUJKV-INIZCTEOSA-N CC1=C(C=CC(=C1)[C@H](C)N(C(=O)O)C(C)(C)C)C(=O)C2=CC=CC3=C2C=CN=C3 Chemical compound CC1=C(C=CC(=C1)[C@H](C)N(C(=O)O)C(C)(C)C)C(=O)C2=CC=CC3=C2C=CN=C3 PACIBGNGCBUJKV-INIZCTEOSA-N 0.000 description 1
• LDXOTWAPQRGHRQ-UHFFFAOYSA-N CC1=CC(=CC(=C1C(=O)C2=CC=CC3=C2C=CN=C3)F)C(C)NNC(=O)OC(C)(C)C Chemical compound CC1=CC(=CC(=C1C(=O)C2=CC=CC3=C2C=CN=C3)F)C(C)NNC(=O)OC(C)(C)C LDXOTWAPQRGHRQ-UHFFFAOYSA-N 0.000 description 1
• WGJQXEPYGOMJNA-UHFFFAOYSA-N CCCCC(C(CCCC)(CCCC)CCCC)OC(=C)[Sn] Chemical compound CCCCC(C(CCCC)(CCCC)CCCC)OC(=C)[Sn] WGJQXEPYGOMJNA-UHFFFAOYSA-N 0.000 description 1
• APLVUEYZVQYNSG-UHFFFAOYSA-N CCOC1=C(C=CC(=C1F)C(=O)C2=CC=CC3=C2C=CN=C3OCC)C(C)N Chemical compound CCOC1=C(C=CC(=C1F)C(=O)C2=CC=CC3=C2C=CN=C3OCC)C(C)N APLVUEYZVQYNSG-UHFFFAOYSA-N 0.000 description 1
• ROHSJUUUPQDWPT-UHFFFAOYSA-N CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C(C=C3F)C(C)N(C(=O)OC(C)(C)C)NC)F Chemical compound CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C(C=C3F)C(C)N(C(=O)OC(C)(C)C)NC)F ROHSJUUUPQDWPT-UHFFFAOYSA-N 0.000 description 1
• RTHAXHGVWSTELZ-UHFFFAOYSA-N CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C(C=C3F)CC(=O)OC(C)(C)C)F Chemical compound CCOC1=NC=CC2=C1C=CC=C2C(=O)C3=C(C=C(C=C3F)CC(=O)OC(C)(C)C)F RTHAXHGVWSTELZ-UHFFFAOYSA-N 0.000 description 1
• QYBDTHKQWTULMJ-UHFFFAOYSA-N COC1=C(C=C2CCN(C2=C1)C#N)Br Chemical compound COC1=C(C=C2CCN(C2=C1)C#N)Br QYBDTHKQWTULMJ-UHFFFAOYSA-N 0.000 description 1
• CHFCTLXKNBROGI-HNNXBMFYSA-N C[C@@H](C1=CC=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)NNC(=O)OC(C)(C)C Chemical compound C[C@@H](C1=CC=C(C=C1)C(=O)C2=CC=CC3=C2C=CN=C3)NNC(=O)OC(C)(C)C CHFCTLXKNBROGI-HNNXBMFYSA-N 0.000 description 1
• XNWHJSVFQIXAHY-UHFFFAOYSA-N C[Mg]C1CCCCC1 Chemical compound C[Mg]C1CCCCC1 XNWHJSVFQIXAHY-UHFFFAOYSA-N 0.000 description 1
• 241000345998 Calamus manan Species 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• XMHJWNRFCYZWAE-UHFFFAOYSA-N ClC1=CN=C(C2=CC=CC(=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)OCC Chemical compound ClC1=CN=C(C2=CC=CC(=C12)C(=O)C1=C(C=C(C=C1F)C(C)NC(OC(C)(C)C)=O)F)OCC XMHJWNRFCYZWAE-UHFFFAOYSA-N 0.000 description 1
• UHULRXKYLCMRAU-UHFFFAOYSA-N ClC=1C=C(C=C(C=1C(=O)C1=C2C=CN=CC2=CC=C1)F)C(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=C(C=1C(=O)C1=C2C=CN=CC2=CC=C1)F)C(C)NC(OC(C)(C)C)=O UHULRXKYLCMRAU-UHFFFAOYSA-N 0.000 description 1
• FLXIMKMTMAPUPO-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C(=CN=C(C2=CC=C1)OCC)C)C(C)(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C(=CN=C(C2=CC=C1)OCC)C)C(C)(C)NC(OC(C)(C)C)=O FLXIMKMTMAPUPO-UHFFFAOYSA-N 0.000 description 1
• ZWNXHPKYFWMIAZ-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C=C(N=C(C2=CC=C1)OCC)C)C(C)(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C=C(N=C(C2=CC=C1)OCC)C)C(C)(C)NC(OC(C)(C)C)=O ZWNXHPKYFWMIAZ-UHFFFAOYSA-N 0.000 description 1
• QVLAQNGNIVVYTG-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)C(C)(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)C(C)(C)NC(OC(C)(C)C)=O QVLAQNGNIVVYTG-UHFFFAOYSA-N 0.000 description 1
• MRUALMOBYJPQTG-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)C(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)C(C)NC(OC(C)(C)C)=O MRUALMOBYJPQTG-UHFFFAOYSA-N 0.000 description 1
• MTLPGMNCDDMSMJ-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)(C)NC(OC(C)(C)C)=O MTLPGMNCDDMSMJ-UHFFFAOYSA-N 0.000 description 1
• QAHHTLXABPCOTF-UHFFFAOYSA-N ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)NC(OC(C)(C)C)=O Chemical compound ClC=1C=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)NC(OC(C)(C)C)=O QAHHTLXABPCOTF-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• 208000003890 Coronary Vasospasm Diseases 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
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• NONHYKZRVHKBPL-UHFFFAOYSA-N FC=1C(=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)NC(OC(C)(C)C)=O)C Chemical compound FC=1C(=C(C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1)C(C)NC(OC(C)(C)C)=O)C NONHYKZRVHKBPL-UHFFFAOYSA-N 0.000 description 1
• JILMVYSKFCJOLJ-AWEZNQCLSA-N FC=1C=C(C=C(C=1C(=O)C1=C2C(=CN=CC2=CC=C1)C)F)[C@H](C)NC(OC(C)(C)C)=O Chemical compound FC=1C=C(C=C(C=1C(=O)C1=C2C(=CN=CC2=CC=C1)C)F)[C@H](C)NC(OC(C)(C)C)=O JILMVYSKFCJOLJ-AWEZNQCLSA-N 0.000 description 1
• PTTLIWBZRZDXEO-UHFFFAOYSA-N FC=1C=C(C=C(C=1C(=O)C1=C2C=CN=CC2=CC=C1)F)C(C)(C)NC(OC(C)(C)C)=O Chemical compound FC=1C=C(C=C(C=1C(=O)C1=C2C=CN=CC2=CC=C1)F)C(C)(C)NC(OC(C)(C)C)=O PTTLIWBZRZDXEO-UHFFFAOYSA-N 0.000 description 1
• IVOJLJXHBKPOLX-JRTLGTJJSA-N FC=1C=C(C=C(C=1C(C1=C2C=CN=CC2=CC=C1)O)F)[C@H](C)NC(OC(C)(C)C)=O Chemical compound FC=1C=C(C=C(C=1C(C1=C2C=CN=CC2=CC=C1)O)F)[C@H](C)NC(OC(C)(C)C)=O IVOJLJXHBKPOLX-JRTLGTJJSA-N 0.000 description 1
• UWQDZSMYMCEQDW-UHFFFAOYSA-N FC=1C=C(CNC(OC(C)(C)C)=O)C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1 Chemical compound FC=1C=C(CNC(OC(C)(C)C)=O)C=CC=1C(=O)C1=C2C=CN=CC2=CC=C1 UWQDZSMYMCEQDW-UHFFFAOYSA-N 0.000 description 1
• 102000008946 Fibrinogen Human genes 0.000 description 1
• 108010049003 Fibrinogen Proteins 0.000 description 1
• 238000005618 Fries rearrangement reaction Methods 0.000 description 1
• 108010010803 Gelatin Proteins 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
• 208000003923 Hereditary Corneal Dystrophies Diseases 0.000 description 1
• 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
• 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
• YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
• CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 102000007330 LDL Lipoproteins Human genes 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 229910010082 LiAlH Inorganic materials 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229940121743 Muscarinic receptor agonist Drugs 0.000 description 1
• 102000003505 Myosin Human genes 0.000 description 1
• 108060008487 Myosin Proteins 0.000 description 1
• 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
• PXZCOJKKGKZMKM-CQSZACIVSA-N N-[(1R)-1-[4-[(1-ethoxyisoquinolin-5-yl)methyl]-3-methoxyphenyl]ethyl]-2,2,2-trifluoroacetamide Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)CC1=C(C=C(C=C1)[C@@H](C)NC(C(F)(F)F)=O)OC PXZCOJKKGKZMKM-CQSZACIVSA-N 0.000 description 1
• RPFQOXNTFKBWBT-KFKHOZABSA-N N-[(1S)-1-[3-(1-ethoxyisoquinoline-5-carbonyl)-2,4-difluorophenyl]ethyl]-2-methylpropane-2-sulfinamide Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1F)[C@H](C)NS(=O)C(C)(C)C)F RPFQOXNTFKBWBT-KFKHOZABSA-N 0.000 description 1
• OZTKENYOFAKTPI-UHFFFAOYSA-N N-[1-(3,5-difluorophenyl)-2-methylpropyl]-2-methylpropane-2-sulfinamide Chemical compound FC=1C=C(C=C(C=1)F)C(C(C)C)NS(=O)C(C)(C)C OZTKENYOFAKTPI-UHFFFAOYSA-N 0.000 description 1
• VMHIRDQGZUABMM-UHFFFAOYSA-N N-[1-[3-(1-ethoxyisoquinoline-5-carbonyl)-2-fluorophenyl]ethyl]-2-methylpropane-2-sulfinamide Chemical compound C(C)OC1=NC=CC2=C(C=CC=C12)C(=O)C=1C(=C(C=CC=1)C(C)NS(=O)C(C)(C)C)F VMHIRDQGZUABMM-UHFFFAOYSA-N 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• 206010056677 Nerve degeneration Diseases 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
• 235000003140 Panax quinquefolius Nutrition 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 244000089486 Phragmites australis subsp australis Species 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 102000018120 Recombinases Human genes 0.000 description 1
• 108010091086 Recombinases Proteins 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
• 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
• 238000000297 Sandmeyer reaction Methods 0.000 description 1
• 241000207929 Scutellaria Species 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 102100037764 Serine/threonine-protein phosphatase PP1-beta catalytic subunit Human genes 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• 238000006619 Stille reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 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
• 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 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
• 101150012828 UPC2 gene Proteins 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 208000033774 Ventricular Remodeling Diseases 0.000 description 1
• 238000007326 Weinreb synthesis reaction Methods 0.000 description 1
• IQIZZRLDHDYNDD-JTQLQIEISA-N [(1S)-1-[4-(4-chloro-1-ethoxyisoquinoline-5-carbonyl)-3,5-difluorophenyl]ethyl]carbamic acid Chemical compound CCOc1ncc(Cl)c2c(cccc12)C(=O)c1c(F)cc(cc1F)[C@H](C)NC(O)=O IQIZZRLDHDYNDD-JTQLQIEISA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• FCEZVPPPKZQQGN-AWEZNQCLSA-N [2,6-difluoro-4-[(1S)-1-(2-methoxyethylamino)ethyl]phenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound FC1=C(C(=CC(=C1)[C@H](C)NCCOC)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC FCEZVPPPKZQQGN-AWEZNQCLSA-N 0.000 description 1
• RAZYMGUKDXWKNC-UHFFFAOYSA-N [2,6-difluoro-4-[1-(2-methylsulfonylethylamino)ethyl]phenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound FC1=C(C(=CC(=C1)C(C)NCCS(=O)(=O)C)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC RAZYMGUKDXWKNC-UHFFFAOYSA-N 0.000 description 1
• QZTCWVAOSZLAKL-UHFFFAOYSA-N [3,5-difluoro-4-(isoquinolin-5-ylmethyl)phenyl] trifluoromethanesulfonate Chemical compound FC(S(=O)(=O)OC1=CC(=C(C(=C1)F)CC1=C2C=CN=CC2=CC=C1)F)(F)F QZTCWVAOSZLAKL-UHFFFAOYSA-N 0.000 description 1
• FWNPXAZBVRQJPP-UHFFFAOYSA-N [4-(1-aminoethyl)-2,6-difluorophenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound NC(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F FWNPXAZBVRQJPP-UHFFFAOYSA-N 0.000 description 1
• LYCRIUGGPDYPFA-UHFFFAOYSA-N [4-(1-aminoethyl)-2-methoxyphenyl]-isoquinolin-5-ylmethanone Chemical compound NC(C)C1=CC(=C(C=C1)C(=O)C1=C2C=CN=CC2=CC=C1)OC LYCRIUGGPDYPFA-UHFFFAOYSA-N 0.000 description 1
• GCDTUXICWAHZAA-UHFFFAOYSA-N [4-(1-aminoethyl)phenyl]-isoquinolin-5-ylmethanone hydrochloride Chemical compound Cl.CC(N)c1ccc(cc1)C(=O)c1cccc2cnccc12 GCDTUXICWAHZAA-UHFFFAOYSA-N 0.000 description 1
• GWANKNLZWJCIEQ-UHFFFAOYSA-N [4-(2-aminopropan-2-yl)-2,6-difluorophenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound NC(C)(C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F GWANKNLZWJCIEQ-UHFFFAOYSA-N 0.000 description 1
• FZBHHVILIJEXJH-CYBMUJFWSA-N [4-[(1R)-1-aminoethyl]-2-methoxyphenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound N[C@H](C)C1=CC(=C(C=C1)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)OC FZBHHVILIJEXJH-CYBMUJFWSA-N 0.000 description 1
• FWNPXAZBVRQJPP-NSHDSACASA-N [4-[(1S)-1-aminoethyl]-2,6-difluorophenyl]-(1-ethoxyisoquinolin-5-yl)methanone Chemical compound N[C@@H](C)C1=CC(=C(C(=C1)F)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC)F FWNPXAZBVRQJPP-NSHDSACASA-N 0.000 description 1
• ZYKGRMNJUAOKCY-UHFFFAOYSA-N [C-]#N.CC(CCCCCCCCC)(C)C Chemical compound [C-]#N.CC(CCCCCCCCC)(C)C ZYKGRMNJUAOKCY-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
• GLRAHDCHUZLKKC-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid;hydrate Chemical compound O.CC#N.OC(=O)C(F)(F)F GLRAHDCHUZLKKC-UHFFFAOYSA-N 0.000 description 1
• CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000533 adrenergic alpha-1 receptor agonist Substances 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229940124277 aminobutyric acid Drugs 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 210000000709 aorta Anatomy 0.000 description 1
• 210000000702 aorta abdominal Anatomy 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
• DLXHBEZQLDJXAH-UHFFFAOYSA-N bis(1-ethoxyisoquinolin-5-yl)methanone Chemical compound C(C)OC1=NC=CC=2C(=CC=CC1=2)C(=O)C1=C2C=CN=C(C2=CC=C1)OCC DLXHBEZQLDJXAH-UHFFFAOYSA-N 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 230000024279 bone resorption Effects 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 210000003678 bronchial smooth muscle cell Anatomy 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000001273 butane Substances 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
• ZZHGIUCYKGFIPV-UHFFFAOYSA-N butylcarbamic acid Chemical compound CCCCNC(O)=O ZZHGIUCYKGFIPV-UHFFFAOYSA-N 0.000 description 1
• 125000006251 butylcarbonyl group Chemical group 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
• 229960004484 carbachol Drugs 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
• 230000006315 carbonylation Effects 0.000 description 1
• 238000005810 carbonylation reaction Methods 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 210000001054 cardiac fibroblast Anatomy 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 230000009989 contractile response Effects 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 208000021921 corneal disease Diseases 0.000 description 1
• 206010011005 corneal dystrophy Diseases 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 201000011634 coronary artery vasospasm Diseases 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical compound NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 1
• URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 description 1
• 239000004913 cyclooctene Substances 0.000 description 1
• 210000004292 cytoskeleton Anatomy 0.000 description 1
• 229960002887 deanol Drugs 0.000 description 1
• 238000006264 debenzylation reaction Methods 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
• 229910000071 diazene Inorganic materials 0.000 description 1
• HTFFABIIOAKIBH-UHFFFAOYSA-N diazinane Chemical compound C1CCNNC1 HTFFABIIOAKIBH-UHFFFAOYSA-N 0.000 description 1
• 239000012972 dimethylethanolamine Substances 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 1
• 229960002435 fasudil Drugs 0.000 description 1
• 229940012952 fibrinogen Drugs 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 235000021550 forms of sugar Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 238000011990 functional testing Methods 0.000 description 1
• 150000002240 furans Chemical class 0.000 description 1
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
• 238000004817 gas chromatography Methods 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 235000008434 ginseng Nutrition 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• 102000053038 human ROCK1 Human genes 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 230000004410 intraocular pressure Effects 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 210000004731 jugular vein Anatomy 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• JORQDGTZGKHEEO-UHFFFAOYSA-N lithium cyanide Chemical compound [Li+].N#[C-] JORQDGTZGKHEEO-UHFFFAOYSA-N 0.000 description 1
• IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000004337 magnesium citrate Substances 0.000 description 1
• 229960005336 magnesium citrate Drugs 0.000 description 1
• 235000002538 magnesium citrate Nutrition 0.000 description 1
• 150000002681 magnesium compounds Chemical class 0.000 description 1
• VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-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
• YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
• FKUUDDGRDRPAQQ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=C[C-]=C1 FKUUDDGRDRPAQQ-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000000472 muscarinic agonist Substances 0.000 description 1
• 210000000651 myofibroblast Anatomy 0.000 description 1
• 230000001114 myogenic effect Effects 0.000 description 1
• IWNGIYKUHTUTJR-UHFFFAOYSA-N n-[(2,4-difluorophenyl)methylidene]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)S(=O)N=CC1=CC=C(F)C=C1F IWNGIYKUHTUTJR-UHFFFAOYSA-N 0.000 description 1
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• 229940100662 nasal drops Drugs 0.000 description 1
• 201000009925 nephrosclerosis Diseases 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 230000009251 neurologic dysfunction Effects 0.000 description 1
• 208000015015 neurological dysfunction Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical group Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 210000001328 optic nerve Anatomy 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
• 229960001802 phenylephrine Drugs 0.000 description 1
• 150000003003 phosphines Chemical class 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229940106205 potassium 20 mg Drugs 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
• 235000011118 potassium hydroxide Nutrition 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 235000012950 rattan cane Nutrition 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229910052703 rhodium Inorganic materials 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• LMYKTNLGBUMKNF-UHFFFAOYSA-N ruthenium(1+) Chemical class [Ru+] LMYKTNLGBUMKNF-UHFFFAOYSA-N 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 210000003518 stress fiber Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• UDXYGLFTKCLYEN-UHFFFAOYSA-N tert-butyl N-[2-(4-bromo-3,5-difluorophenyl)propan-2-yl]carbamate Chemical compound BrC1=C(C=C(C=C1F)C(C)(C)NC(OC(C)(C)C)=O)F UDXYGLFTKCLYEN-UHFFFAOYSA-N 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 description 1
• WXRGABKACDFXMG-UHFFFAOYSA-N trimethylborane Chemical compound CB(C)C WXRGABKACDFXMG-UHFFFAOYSA-N 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 238000005550 wet granulation Methods 0.000 description 1