OA12970A - 2-aminocarbonyl-quinoline compounds as platelet adenosine diphosphate receptor antagonists. - Google Patents

Info

Publication number

OA12970A

OA12970A OA1200500175A OA1200500175A OA12970A OA 12970 A OA12970 A OA 12970A OA 1200500175 A OA1200500175 A OA 1200500175A OA 1200500175 A OA1200500175 A OA 1200500175A OA 12970 A OA12970 A OA 12970A

Authority

OA

OAPI

Prior art keywords

alkyl

hydrogen

aminocarbonyl

aralkyl

carboxy

Prior art date

2002-12-11

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000719 purinergic P2Y receptor antagonist Substances 0.000 title description 3
• ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 284
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• -1 aralkoxycarbonyl Chemical group 0.000 claims description 338
• 229910052739 hydrogen Inorganic materials 0.000 claims description 213
• 239000001257 hydrogen Substances 0.000 claims description 213
• 125000000217 alkyl group Chemical group 0.000 claims description 211
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 210
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 163
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 128
• 125000001188 haloalkyl group Chemical group 0.000 claims description 112
• ZTQNUTNKGQGWCM-UHFFFAOYSA-N 2-methoxyquinoline Chemical compound C1=CC=CC2=NC(OC)=CC=C21 ZTQNUTNKGQGWCM-UHFFFAOYSA-N 0.000 claims description 100
• 125000003118 aryl group Chemical group 0.000 claims description 82
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 81
• 125000005843 halogen group Chemical group 0.000 claims description 78
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 69
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 66
• 239000000203 mixture Substances 0.000 claims description 63
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 42
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 36
• IDPWXVBDDIYDKT-UHFFFAOYSA-N 2-phenoxyquinoline Chemical compound C=1C=C2C=CC=CC2=NC=1OC1=CC=CC=C1 IDPWXVBDDIYDKT-UHFFFAOYSA-N 0.000 claims description 35
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
• 125000002947 alkylene group Chemical group 0.000 claims description 34
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 29
• 125000003545 alkoxy group Chemical group 0.000 claims description 29
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 29
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 25
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 22
• 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 20
• 150000005840 aryl radicals Chemical class 0.000 claims description 20
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 20
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 20
• 230000001732 thrombotic effect Effects 0.000 claims description 20
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 19
• 125000004414 alkyl thio group Chemical group 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 18
• 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 18
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
• VGJWVEYTYIBXIA-UHFFFAOYSA-N 2,2,2-trifluoroethane-1,1-diol Chemical compound OC(O)C(F)(F)F VGJWVEYTYIBXIA-UHFFFAOYSA-N 0.000 claims description 14
• NWIAYUZWWLSLBI-UHFFFAOYSA-N 2-phenylmethoxyquinoline Chemical compound C=1C=C2C=CC=CC2=NC=1OCC1=CC=CC=C1 NWIAYUZWWLSLBI-UHFFFAOYSA-N 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 125000004104 aryloxy group Chemical group 0.000 claims description 10
• 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 9
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 9
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 9
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 9
• 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 9
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 7
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 7
• FSEXLNMNADBYJU-UHFFFAOYSA-N 2-phenylquinoline Chemical compound C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=N1 FSEXLNMNADBYJU-UHFFFAOYSA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 4
• UZUOATDJYUTEOA-UHFFFAOYSA-N 4-[[6-chloro-7-methyl-4-[(2-methyl-1,3-thiazol-4-yl)methoxy]quinoline-2-carbonyl]amino]-5-(4-ethoxycarbonylpiperazin-1-yl)-5-oxopentanoic acid Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(CCC(O)=O)NC(=O)C1=CC(OCC=2N=C(C)SC=2)=C(C=C(Cl)C(C)=C2)C2=N1 UZUOATDJYUTEOA-UHFFFAOYSA-N 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• UNHIHSPMHQKWCJ-UHFFFAOYSA-N ethyl 4-[2-[(8-methoxy-4-phenylmethoxyquinoline-2-carbonyl)amino]-5-oxo-5-phenylmethoxypentanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(NC(=O)C=1N=C2C(OC)=CC=CC2=C(OCC=2C=CC=CC=2)C=1)CCC(=O)OCC1=CC=CC=C1 UNHIHSPMHQKWCJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 17
• 238000000034 method Methods 0.000 abstract description 45
• XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 abstract description 29
• XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 abstract description 28
• 230000008569 process Effects 0.000 abstract description 5
• 239000003146 anticoagulant agent Substances 0.000 abstract description 4
• 229960004676 antithrombotic agent Drugs 0.000 abstract description 3
• 239000003112 inhibitor Substances 0.000 abstract description 3
• 230000002194 synthesizing effect Effects 0.000 abstract 1
• 150000003254 radicals Chemical class 0.000 description 76
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
• 239000011541 reaction mixture Substances 0.000 description 46
• 238000006243 chemical reaction Methods 0.000 description 37
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• 239000000243 solution Substances 0.000 description 36
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 101000621371 Homo sapiens WD and tetratricopeptide repeats protein 1 Proteins 0.000 description 24
• 101000892274 Human adenovirus C serotype 2 Adenovirus death protein Proteins 0.000 description 24
• 101000820656 Rattus norvegicus Seminal vesicle secretory protein 4 Proteins 0.000 description 24
• 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 24
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 18
• 208000007536 Thrombosis Diseases 0.000 description 16
• 229940093499 ethyl acetate Drugs 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 239000000651 prodrug Substances 0.000 description 15
• 229940002612 prodrug Drugs 0.000 description 15
• 150000003839 salts Chemical class 0.000 description 15
• 239000007787 solid Substances 0.000 description 15
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 14
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 239000012267 brine Substances 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• 241000700159 Rattus Species 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 238000003818 flash chromatography Methods 0.000 description 10
• 238000002955 isolation Methods 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• 102000007466 Purinergic P2 Receptors Human genes 0.000 description 9
• 108010085249 Purinergic P2 Receptors Proteins 0.000 description 9
• 230000002776 aggregation Effects 0.000 description 9
• 238000004220 aggregation Methods 0.000 description 9
• 238000009739 binding Methods 0.000 description 9
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• 235000019198 oils Nutrition 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 239000000010 aprotic solvent Substances 0.000 description 8
• 230000027455 binding Effects 0.000 description 8
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
• 108010035532 Collagen Proteins 0.000 description 7
• 102000008186 Collagen Human genes 0.000 description 7
• 235000011054 acetic acid Nutrition 0.000 description 7
• 229960000583 acetic acid Drugs 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 229920001436 collagen Polymers 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 229940073584 methylene chloride Drugs 0.000 description 7
• 230000010118 platelet activation Effects 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000011282 treatment Methods 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
• 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 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 239000008187 granular material Substances 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 238000005160 1H NMR spectroscopy Methods 0.000 description 5
• 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 5
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 239000005557 antagonist Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 238000009835 boiling Methods 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• JYASQADVXZBDBP-UHFFFAOYSA-N ethyl 4-[2-amino-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)C(N)CCC(=O)OC(C)(C)C)CC1 JYASQADVXZBDBP-UHFFFAOYSA-N 0.000 description 5
• 238000000605 extraction Methods 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 239000008188 pellet Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 5
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 5
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• 108090000190 Thrombin Proteins 0.000 description 4
• WLMZTKAZJUWXCB-JLOOSCHCSA-N [(2r,3s,4r,5r)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphoryl hydrogen phosphate Chemical compound C12=NC(SC)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO[33P](O)(=O)O[33P](O)(O)=O)[C@@H](O)[C@H]1O WLMZTKAZJUWXCB-JLOOSCHCSA-N 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
• 239000011575 calcium Substances 0.000 description 4
• 229910052791 calcium Inorganic materials 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 150000007530 organic bases Chemical class 0.000 description 4
• 238000005897 peptide coupling reaction Methods 0.000 description 4
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
• 229920000053 polysorbate 80 Polymers 0.000 description 4
• 229940068968 polysorbate 80 Drugs 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 238000004007 reversed phase HPLC Methods 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• 229960004072 thrombin Drugs 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• VUKHRCOPMVPBJV-UHFFFAOYSA-N 7-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(C)=CC=C21 VUKHRCOPMVPBJV-UHFFFAOYSA-N 0.000 description 3
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 3
• 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 230000000996 additive effect Effects 0.000 description 3
• 238000010640 amide synthesis reaction Methods 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 3
• 229960003009 clopidogrel Drugs 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 3
• KPWMOVKJWMPHGC-UHFFFAOYSA-N ethyl 4-[5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(CCC(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 KPWMOVKJWMPHGC-UHFFFAOYSA-N 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• KDNMQEWSPXSMDB-UHFFFAOYSA-N methyl 6-chloro-7-methyl-4-oxo-3h-quinoline-2-carboxylate Chemical compound CC1=C(Cl)C=C2C(=O)CC(C(=O)OC)=NC2=C1 KDNMQEWSPXSMDB-UHFFFAOYSA-N 0.000 description 3
• PNQIEWPPSCIQJF-UHFFFAOYSA-N methyl 7-methyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(C)=CC2=NC(C(=O)OC)=CC(O)=C21 PNQIEWPPSCIQJF-UHFFFAOYSA-N 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 239000003208 petroleum Substances 0.000 description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
• 210000002381 plasma Anatomy 0.000 description 3
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
• 239000003586 protic polar solvent Substances 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 125000003107 substituted aryl group Chemical group 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 238000010626 work up procedure Methods 0.000 description 3
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• FOYMVHMUBKHXLY-UHFFFAOYSA-N 2,4-dichloro-3-methylaniline Chemical compound CC1=C(Cl)C=CC(N)=C1Cl FOYMVHMUBKHXLY-UHFFFAOYSA-N 0.000 description 2
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• NFANKIOZMXAOQA-UHFFFAOYSA-N 4-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C=12C=CC=CC2=NC(C(=O)O)=CC=1OCC1=CC=CC=C1 NFANKIOZMXAOQA-UHFFFAOYSA-N 0.000 description 2
• WUZMBUFJMJXSKR-UHFFFAOYSA-N 6-chloro-7-methyl-4-oxo-3h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)CC(=O)C2=C1C=C(C)C(Cl)=C2 WUZMBUFJMJXSKR-UHFFFAOYSA-N 0.000 description 2
• XQWCILGCSOTHNP-UHFFFAOYSA-N 6-methoxykynurenic acid Natural products N1=C(C(O)=O)C=C(O)C2=CC(OC)=CC=C21 XQWCILGCSOTHNP-UHFFFAOYSA-N 0.000 description 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
• 208000005189 Embolism Diseases 0.000 description 2
• 108010049003 Fibrinogen Proteins 0.000 description 2
• 102000008946 Fibrinogen Human genes 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
• 108091006027 G proteins Proteins 0.000 description 2
• 102000030782 GTP binding Human genes 0.000 description 2
• 108091000058 GTP-Binding Proteins 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 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
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 208000018262 Peripheral vascular disease Diseases 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
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
• 102000003923 Protein Kinase C Human genes 0.000 description 2
• 108090000315 Protein Kinase C Proteins 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 101150045640 VWF gene Proteins 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 108060000200 adenylate cyclase Proteins 0.000 description 2
• 102000030621 adenylate cyclase Human genes 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• MDVWXUPGKCAUFT-UHFFFAOYSA-N benzyl 4-phenylmethoxyquinoline-2-carboxylate Chemical compound C=1C(OCC=2C=CC=CC=2)=C2C=CC=CC2=NC=1C(=O)OCC1=CC=CC=C1 MDVWXUPGKCAUFT-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• 239000012148 binding buffer Substances 0.000 description 2
• 229960001948 caffeine Drugs 0.000 description 2
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
• 229920003086 cellulose ether Polymers 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 2
• 229940012952 fibrinogen Drugs 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 150000002334 glycols Chemical class 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 150000002513 isocyanates Chemical class 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 210000004731 jugular vein Anatomy 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• YKUCHDXIBAQWSF-UHFFFAOYSA-N methyl 3-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(O)=C1 YKUCHDXIBAQWSF-UHFFFAOYSA-N 0.000 description 2
• QARINEVIJSEOJL-UHFFFAOYSA-N methyl 5-methyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound CC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 QARINEVIJSEOJL-UHFFFAOYSA-N 0.000 description 2
• XKRIJFVCZPNGFV-UHFFFAOYSA-N methyl 6,8-dichloro-7-methyl-4-oxo-3h-quinoline-2-carboxylate Chemical compound CC1=C(Cl)C=C2C(=O)CC(C(=O)OC)=NC2=C1Cl XKRIJFVCZPNGFV-UHFFFAOYSA-N 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000000466 oxiranyl group Chemical group 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 239000003880 polar aprotic solvent Substances 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 229920006395 saturated elastomer Polymers 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
• 230000007781 signaling event Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000001052 transient effect Effects 0.000 description 2
• 125000001425 triazolyl group Chemical group 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 210000000264 venule Anatomy 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• WBNZUUIFTPNYRN-UHFFFAOYSA-N 1,3-dichloro-2-methyl-4-nitrobenzene Chemical compound CC1=C(Cl)C=CC([N+]([O-])=O)=C1Cl WBNZUUIFTPNYRN-UHFFFAOYSA-N 0.000 description 1
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
• PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 1
• 125000006516 2-(benzyloxy)ethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• UINLLRLLXBYTEC-UHFFFAOYSA-N 2-[(2-methoxycarbonyl-4-oxo-1h-quinolin-5-yl)amino]acetic acid Chemical compound OC(=O)CNC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 UINLLRLLXBYTEC-UHFFFAOYSA-N 0.000 description 1
• XHUCFQSRGQQMBY-UHFFFAOYSA-N 2-[(2-methoxycarbonyl-4-oxo-1h-quinolin-6-yl)oxy]acetic acid Chemical compound C1=C(OCC(O)=O)C=CC2=NC(C(=O)OC)=CC(O)=C21 XHUCFQSRGQQMBY-UHFFFAOYSA-N 0.000 description 1
• SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• IJRKANNOPXMZSG-SSPAHAAFSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O IJRKANNOPXMZSG-SSPAHAAFSA-N 0.000 description 1
• DIHIDGCAZGNJTG-UHFFFAOYSA-N 2-methoxycarbonyl-4-oxo-1h-quinoline-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=NC(C(=O)OC)=CC(O)=C21 DIHIDGCAZGNJTG-UHFFFAOYSA-N 0.000 description 1
• NIPCZXOCJCMYQG-UHFFFAOYSA-N 2-methoxycarbonyl-4-oxo-1h-quinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=NC(C(=O)OC)=CC(O)=C21 NIPCZXOCJCMYQG-UHFFFAOYSA-N 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• MOIUVBZFQQOLFV-UHFFFAOYSA-N 3-amino-4-(4-ethoxycarbonylpiperazin-1-yl)-4-oxobutanoic acid Chemical compound CCOC(=O)N1CCN(C(=O)C(N)CC(O)=O)CC1 MOIUVBZFQQOLFV-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
• DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• MHNJPWUAEZIRQL-UHFFFAOYSA-N 4-[(2-methoxycarbonyl-4-oxo-1h-quinolin-5-yl)oxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 MHNJPWUAEZIRQL-UHFFFAOYSA-N 0.000 description 1
• LXJRTIXWOROFFD-UHFFFAOYSA-N 4-amino-5-(4-ethoxycarbonylpiperazin-1-yl)-5-oxopentanoic acid Chemical compound CCOC(=O)N1CCN(C(=O)C(N)CCC(O)=O)CC1 LXJRTIXWOROFFD-UHFFFAOYSA-N 0.000 description 1
• HIHCTGNZNHSZPP-UHFFFAOYSA-N 4-chloro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1Cl HIHCTGNZNHSZPP-UHFFFAOYSA-N 0.000 description 1
• OHNSLONXAWKGPO-UHFFFAOYSA-N 4-chloro-7-methylquinoline-2-carboxylic acid Chemical compound ClC1=CC(C(O)=O)=NC2=CC(C)=CC=C21 OHNSLONXAWKGPO-UHFFFAOYSA-N 0.000 description 1
• XDHVXNYIJMSNIQ-UHFFFAOYSA-N 4-chloroquinoline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC(Cl)=C21 XDHVXNYIJMSNIQ-UHFFFAOYSA-N 0.000 description 1
• BJHDMLKALWQTSL-UHFFFAOYSA-N 4-hydroxy-1-[2-[(2-methoxycarbonyl-4-oxo-1h-quinolin-7-yl)oxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound C=1C2=NC(C(=O)OC)=CC(O)=C2C=CC=1OCCN1CC(O)CC1C(O)=O BJHDMLKALWQTSL-UHFFFAOYSA-N 0.000 description 1
• KQFRZQHCZNAUOS-UHFFFAOYSA-N 4-hydroxy-6-nitroquinoline-2-carboxylic acid Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 KQFRZQHCZNAUOS-UHFFFAOYSA-N 0.000 description 1
• BXZSKDOPGDPDEG-UHFFFAOYSA-N 4-hydroxy-8-methoxyquinaldic acid Chemical compound N1C(C(O)=O)=CC(=O)C2=C1C(OC)=CC=C2 BXZSKDOPGDPDEG-UHFFFAOYSA-N 0.000 description 1
• SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
• SNKUZRDGFUABLR-UHFFFAOYSA-N 4-oxo-6-(trifluoromethoxy)-1h-quinoline-2-carboxylic acid Chemical compound C1=C(OC(F)(F)F)C=CC2=NC(C(=O)O)=CC(O)=C21 SNKUZRDGFUABLR-UHFFFAOYSA-N 0.000 description 1
• RSWAHMHVZWQOBB-UHFFFAOYSA-N 4-oxo-6-phenylmethoxy-1h-quinoline-2-carboxylic acid Chemical compound C1=CC2=NC(C(=O)O)=CC(O)=C2C=C1OCC1=CC=CC=C1 RSWAHMHVZWQOBB-UHFFFAOYSA-N 0.000 description 1
• QGUUPWDLDJHREY-UHFFFAOYSA-N 4-oxo-6-propan-2-yloxy-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(OC(C)C)=CC=C21 QGUUPWDLDJHREY-UHFFFAOYSA-N 0.000 description 1
• BPADKUBXVLRXKX-UHFFFAOYSA-N 4-oxo-7-(trifluoromethoxy)-1h-quinoline-2-carboxylic acid Chemical compound C1=C(OC(F)(F)F)C=C2NC(C(=O)O)=CC(=O)C2=C1 BPADKUBXVLRXKX-UHFFFAOYSA-N 0.000 description 1
• WIRWWNYJQQTWAH-UHFFFAOYSA-N 4-oxo-7-(trifluoromethyl)-1h-quinoline-2-carboxylic acid Chemical compound C1=CC(C(F)(F)F)=CC2=NC(C(=O)O)=CC(O)=C21 WIRWWNYJQQTWAH-UHFFFAOYSA-N 0.000 description 1
• IBFCOSJQDAGGIU-UHFFFAOYSA-N 4-oxo-7-phenylmethoxy-1h-quinoline-2-carboxylic acid Chemical compound C=1C2=NC(C(=O)O)=CC(O)=C2C=CC=1OCC1=CC=CC=C1 IBFCOSJQDAGGIU-UHFFFAOYSA-N 0.000 description 1
• NNUNAEAYSSIYJY-UHFFFAOYSA-N 4-oxo-7-propoxy-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(OCCC)=CC=C21 NNUNAEAYSSIYJY-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• XDOJJNMXTWGQCG-UHFFFAOYSA-N 5-(4-ethoxy-4-oxobutoxy)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(OCCCC(=O)OCC)=CC=CC2=N1 XDOJJNMXTWGQCG-UHFFFAOYSA-N 0.000 description 1
• QFWBSWNLDCXLHB-UHFFFAOYSA-N 5-(carboxymethylamino)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(NCC(=O)O)=CC=CC2=N1 QFWBSWNLDCXLHB-UHFFFAOYSA-N 0.000 description 1
• HWDJOTREUZYNRX-UHFFFAOYSA-N 5-(diacetylamino)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(N(C(C)=O)C(=O)C)=CC=CC2=N1 HWDJOTREUZYNRX-UHFFFAOYSA-N 0.000 description 1
• MPMLVDMFTJGKFP-UHFFFAOYSA-N 5-(hydroxymethoxy)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(OCO)=CC=CC2=N1 MPMLVDMFTJGKFP-UHFFFAOYSA-N 0.000 description 1
• YDNCBFOCOUQJFG-UHFFFAOYSA-N 5-amino-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(N)=CC=CC2=N1 YDNCBFOCOUQJFG-UHFFFAOYSA-N 0.000 description 1
• VNTWFLFOLQXWST-UHFFFAOYSA-N 5-ethoxycarbonyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(C(=O)OCC)=CC=CC2=N1 VNTWFLFOLQXWST-UHFFFAOYSA-N 0.000 description 1
• HVSFRCFUUIRDTD-UHFFFAOYSA-N 5-fluoro-6-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=C(F)C(C)=CC=C21 HVSFRCFUUIRDTD-UHFFFAOYSA-N 0.000 description 1
• ODRYOTUXSMPUCC-UHFFFAOYSA-N 5-hydroxy-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC=CC2=NC(C(=O)O)=CC(O)=C21 ODRYOTUXSMPUCC-UHFFFAOYSA-N 0.000 description 1
• BBUTUPXHFJJRPY-UHFFFAOYSA-N 5-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C(C)=CC=CC2=N1 BBUTUPXHFJJRPY-UHFFFAOYSA-N 0.000 description 1
• HJNKNTGLQXFSON-UHFFFAOYSA-N 5-nitro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound [O-][N+](=O)C1=CC=CC2=NC(C(=O)O)=CC(O)=C21 HJNKNTGLQXFSON-UHFFFAOYSA-N 0.000 description 1
• ZOMGDODDPHQOIW-UHFFFAOYSA-N 5-o-ethyl 2-o-methyl 4-oxo-1h-quinoline-2,5-dicarboxylate Chemical compound COC(=O)C1=CC(O)=C2C(C(=O)OCC)=CC=CC2=N1 ZOMGDODDPHQOIW-UHFFFAOYSA-N 0.000 description 1
• FSORDQBTOYXMPE-UHFFFAOYSA-N 6,7-dichloro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=C(Cl)C(Cl)=CC2=NC(C(=O)O)=CC(O)=C21 FSORDQBTOYXMPE-UHFFFAOYSA-N 0.000 description 1
• JSJGHNQOTLGAQL-UHFFFAOYSA-N 6-(carboxymethoxy)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(OCC(=O)O)=CC=C21 JSJGHNQOTLGAQL-UHFFFAOYSA-N 0.000 description 1
• LXYOVYNQVWZBCJ-UHFFFAOYSA-N 6-(diethylaminomethyl)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(CN(CC)CC)=CC=C21 LXYOVYNQVWZBCJ-UHFFFAOYSA-N 0.000 description 1
• GIDZHQGDZIVANV-UHFFFAOYSA-N 6-(dimethylamino)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(N(C)C)=CC=C21 GIDZHQGDZIVANV-UHFFFAOYSA-N 0.000 description 1
• PVEUZCNAYPBTDG-UHFFFAOYSA-N 6-acetyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(C(=O)C)=CC=C21 PVEUZCNAYPBTDG-UHFFFAOYSA-N 0.000 description 1
• QZEFSCNILAKRAL-UHFFFAOYSA-N 6-amino-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(N)=CC=C21 QZEFSCNILAKRAL-UHFFFAOYSA-N 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• FBHYBXRWVNVMRY-UHFFFAOYSA-N 6-chloro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 FBHYBXRWVNVMRY-UHFFFAOYSA-N 0.000 description 1
• JVVZOMVQFKXXOQ-UHFFFAOYSA-N 6-chloro-7-methyl-4-oxo-1H-quinoline-2-carboxamide Chemical compound NC(=O)C1=NC2=CC(=C(C=C2C(=C1)O)Cl)C JVVZOMVQFKXXOQ-UHFFFAOYSA-N 0.000 description 1
• QGQNZNBUBDHFFB-UHFFFAOYSA-N 6-chloro-7-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C=C(Cl)C(C)=CC2=N1 QGQNZNBUBDHFFB-UHFFFAOYSA-N 0.000 description 1
• XLHIQTFZEQSLGJ-UHFFFAOYSA-N 6-ethoxy-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(O)C2=CC(OCC)=CC=C21 XLHIQTFZEQSLGJ-UHFFFAOYSA-N 0.000 description 1
• RHDREWQIVYIOGH-UHFFFAOYSA-N 6-fluoro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound FC1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 RHDREWQIVYIOGH-UHFFFAOYSA-N 0.000 description 1
• HEEUEAVHQLRGGS-UHFFFAOYSA-N 6-fluoro-7-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC(=O)C1=CC(O)=C2C=C(F)C(C)=CC2=N1 HEEUEAVHQLRGGS-UHFFFAOYSA-N 0.000 description 1
• OOOBICRIERYUDE-UHFFFAOYSA-N 6-methylsulfanyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1C(C(O)=O)=CC(=O)C2=CC(SC)=CC=C21 OOOBICRIERYUDE-UHFFFAOYSA-N 0.000 description 1
• FTNGTLSTVCQETR-UHFFFAOYSA-N 7-(carboxymethoxy)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(OCC(=O)O)=CC=C21 FTNGTLSTVCQETR-UHFFFAOYSA-N 0.000 description 1
• XTWIFEGDVWSVFW-UHFFFAOYSA-N 7-(hydroxymethyl)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(CO)=CC=C21 XTWIFEGDVWSVFW-UHFFFAOYSA-N 0.000 description 1
• VPMGGGLRCZSFDX-UHFFFAOYSA-N 7-[2-(diethylamino)ethoxy]-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(OCCN(CC)CC)=CC=C21 VPMGGGLRCZSFDX-UHFFFAOYSA-N 0.000 description 1
• ITZALMYWLVXMGK-UHFFFAOYSA-N 7-acetyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(C(=O)C)=CC=C21 ITZALMYWLVXMGK-UHFFFAOYSA-N 0.000 description 1
• DGJNOQNOMLMGQD-UHFFFAOYSA-N 7-bromo-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=CC(Br)=CC2=NC(C(=O)O)=CC(O)=C21 DGJNOQNOMLMGQD-UHFFFAOYSA-N 0.000 description 1
• VWJHXNPIPXHWRI-UHFFFAOYSA-N 7-chloro-6-fluoro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=C(F)C(Cl)=CC2=NC(C(=O)O)=CC(O)=C21 VWJHXNPIPXHWRI-UHFFFAOYSA-N 0.000 description 1
• ZDPZMPRVICWFEP-UHFFFAOYSA-N 7-chloro-6-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=C(C(O)=O)N=C2C=C(Cl)C(C)=CC2=C1O ZDPZMPRVICWFEP-UHFFFAOYSA-N 0.000 description 1
• YXILJBKGJDUYAG-UHFFFAOYSA-N 7-cyano-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=CC(C#N)=CC2=NC(C(=O)O)=CC(O)=C21 YXILJBKGJDUYAG-UHFFFAOYSA-N 0.000 description 1
• JUQPPCMGDXBUFQ-UHFFFAOYSA-N 7-methoxy-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound OC1=CC(C(O)=O)=NC2=CC(OC)=CC=C21 JUQPPCMGDXBUFQ-UHFFFAOYSA-N 0.000 description 1
• IQRAMWTVXIQPPW-UHFFFAOYSA-N 7-nitro-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1=CC([N+]([O-])=O)=CC2=NC(C(=O)O)=CC(O)=C21 IQRAMWTVXIQPPW-UHFFFAOYSA-N 0.000 description 1
• JFWIAQNNAPXWLS-UHFFFAOYSA-N 8-methoxy-4-oxo-1H-quinoline-2-carboxylic acid methyl ester Chemical compound C1=CC(OC)=C2NC(C(=O)OC)=CC(=O)C2=C1 JFWIAQNNAPXWLS-UHFFFAOYSA-N 0.000 description 1
• ZLKGGEBOALGXJZ-UHFFFAOYSA-N 8-methoxyquinoline Chemical compound C1=CN=C2C(OC)=CC=CC2=C1 ZLKGGEBOALGXJZ-UHFFFAOYSA-N 0.000 description 1
• ADSHTOPIOBVQEW-UHFFFAOYSA-N 8-methyl-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1C(C(O)=O)=CC(=O)C2=C1C(C)=CC=C2 ADSHTOPIOBVQEW-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 206010002388 Angina unstable Diseases 0.000 description 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 102000007347 Apyrase Human genes 0.000 description 1
• 108010007730 Apyrase Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 101800003265 Beta-thromboglobulin Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 101100001686 Burkholderia cepacia andR gene Proteins 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• QSIURGSZKMASEF-UHFFFAOYSA-N C1=CC=CC2=C(O)C(=O)C(C(=O)O)N=C21 Chemical compound C1=CC=CC2=C(O)C(=O)C(C(=O)O)N=C21 QSIURGSZKMASEF-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 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
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
• 206010051055 Deep vein thrombosis Diseases 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
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 108010014172 Factor V Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 102100036154 Platelet basic protein Human genes 0.000 description 1
• 102000004211 Platelet factor 4 Human genes 0.000 description 1
• 108090000778 Platelet factor 4 Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
• 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• 206010037549 Purpura Diseases 0.000 description 1
• 241001672981 Purpura Species 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
• 206010040621 Shunt occlusion Diseases 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 241000282898 Sus scrofa Species 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
• 208000005485 Thrombocytosis Diseases 0.000 description 1
• 208000001435 Thromboembolism Diseases 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 102000014384 Type C Phospholipases Human genes 0.000 description 1
• 108010079194 Type C Phospholipases Proteins 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• 206010057469 Vascular stenosis Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 208000012346 Venoocclusive disease Diseases 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 102100029469 WD repeat and HMG-box DNA-binding protein 1 Human genes 0.000 description 1
• 101710097421 WD repeat and HMG-box DNA-binding protein 1 Proteins 0.000 description 1
• 238000006959 Williamson synthesis reaction Methods 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• WLMZTKAZJUWXCB-KQYNXXCUSA-N [(2r,3s,4r,5r)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound C12=NC(SC)=NC(N)=C2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O WLMZTKAZJUWXCB-KQYNXXCUSA-N 0.000 description 1
• ZLIAJZQKKBOFJR-WOUKDFQISA-N [[[[(2r,3s,4r,5r)-5-(6-amino-2-propylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-dichloromethyl]phosphonic acid Chemical compound C12=NC(SCCC)=NC(N)=C2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)C(Cl)(Cl)P(O)(O)=O)[C@@H](O)[C@H]1O ZLIAJZQKKBOFJR-WOUKDFQISA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 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
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 229960001456 adenosine triphosphate Drugs 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 125000005121 aminocarbonylalkoxy group Chemical group 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 230000002744 anti-aggregatory effect Effects 0.000 description 1
• 230000002785 anti-thrombosis Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 210000000702 aorta abdominal Anatomy 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 206010003230 arteritis Diseases 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-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
• 229960003237 betaine Drugs 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 239000010836 blood and blood product Substances 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 229940125691 blood product Drugs 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 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
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• PAEBIVWUMLRPSK-IDTAVKCVSA-N cangrelor Chemical compound C1=NC=2C(NCCSC)=NC(SCCC(F)(F)F)=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)C(Cl)(Cl)P(O)(O)=O)[C@@H](O)[C@H]1O PAEBIVWUMLRPSK-IDTAVKCVSA-N 0.000 description 1
• 229960001080 cangrelor Drugs 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 210000001715 carotid artery Anatomy 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 230000003399 chemotactic effect Effects 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• HGAZMNJKRQFZKS-UHFFFAOYSA-N chloroethene;ethenyl acetate Chemical compound ClC=C.CC(=O)OC=C HGAZMNJKRQFZKS-UHFFFAOYSA-N 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 230000015271 coagulation Effects 0.000 description 1
• 238000005345 coagulation Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 239000012059 conventional drug carrier Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000013171 endarterectomy Methods 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• NJSUFZNXBBXAAC-UHFFFAOYSA-N ethanol;toluene Chemical compound CCO.CC1=CC=CC=C1 NJSUFZNXBBXAAC-UHFFFAOYSA-N 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• OPEUHWXSYLEAOD-UHFFFAOYSA-N ethyl 4-(2,6-diaminohexanoyl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)C(N)CCCCN)CC1 OPEUHWXSYLEAOD-UHFFFAOYSA-N 0.000 description 1
• KCHOGKXEDHAWPF-UHFFFAOYSA-N ethyl 4-(2-amino-3-methylbutanoyl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)C(N)C(C)C)CC1 KCHOGKXEDHAWPF-UHFFFAOYSA-N 0.000 description 1
• GKNUOVITASQZAQ-UHFFFAOYSA-N ethyl 4-(2-amino-3-phenylpropanoyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(N)CC1=CC=CC=C1 GKNUOVITASQZAQ-UHFFFAOYSA-N 0.000 description 1
• XGFPBYYVRBDELQ-UHFFFAOYSA-N ethyl 4-(2-amino-4-oxo-4-phenylmethoxybutanoyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(N)CC(=O)OCC1=CC=CC=C1 XGFPBYYVRBDELQ-UHFFFAOYSA-N 0.000 description 1
• WWZMQFLPHXKKEK-UHFFFAOYSA-N ethyl 4-(2-amino-5-methoxy-5-oxopentanoyl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)C(N)CCC(=O)OC)CC1 WWZMQFLPHXKKEK-UHFFFAOYSA-N 0.000 description 1
• ORVDCDZVFVOEMA-UHFFFAOYSA-N ethyl 4-(2-aminoacetyl)-2-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)CN)CC1C ORVDCDZVFVOEMA-UHFFFAOYSA-N 0.000 description 1
• YBDGODZBHMDQRK-UHFFFAOYSA-N ethyl 4-(2-aminoacetyl)-3-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)CN)C(C)C1 YBDGODZBHMDQRK-UHFFFAOYSA-N 0.000 description 1
• LYIBNYLYLUACLT-UHFFFAOYSA-N ethyl 4-(2-aminoacetyl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(=O)CN)CC1 LYIBNYLYLUACLT-UHFFFAOYSA-N 0.000 description 1
• BTYKYRUKSMMQLT-UHFFFAOYSA-N ethyl 4-[2-[(4-oxo-1h-quinoline-2-carbonyl)amino]acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)CNC(=O)C1=CC(O)=C(C=CC=C2)C2=N1 BTYKYRUKSMMQLT-UHFFFAOYSA-N 0.000 description 1
• PCNIQWGASUGNKK-UHFFFAOYSA-N ethyl 4-[2-[(4-phenylmethoxyquinoline-2-carbonyl)amino]acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)CNC(=O)C1=CC(OCC=2C=CC=CC=2)=C(C=CC=C2)C2=N1 PCNIQWGASUGNKK-UHFFFAOYSA-N 0.000 description 1
• MJNYHYCJLBTDKY-UHFFFAOYSA-N ethyl 4-[2-amino-6-[(2-chlorophenyl)methoxycarbonylamino]hexanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(N)CCCCNC(=O)OCC1=CC=CC=C1Cl MJNYHYCJLBTDKY-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
• 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000020764 fibrinolysis Effects 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 125000005291 haloalkenyloxy group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 230000002949 hemolytic effect Effects 0.000 description 1
• 208000031169 hemorrhagic disease Diseases 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229960002885 histidine Drugs 0.000 description 1
• 229940106780 human fibrinogen Drugs 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 238000012423 maintenance Methods 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
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 1
• UUWVRYCGVIPOFC-UHFFFAOYSA-N methyl 3-hydroxyquinoline-2-carboxylate Chemical compound C1=CC=C2C=C(O)C(C(=O)OC)=NC2=C1 UUWVRYCGVIPOFC-UHFFFAOYSA-N 0.000 description 1
• NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
• UUTODJBXAJLMDD-UHFFFAOYSA-N methyl 4-oxo-6-(trifluoromethoxy)-1h-quinoline-2-carboxylate Chemical compound C1=C(OC(F)(F)F)C=CC2=NC(C(=O)OC)=CC(O)=C21 UUTODJBXAJLMDD-UHFFFAOYSA-N 0.000 description 1
• ISEUSWBMFAUWGC-UHFFFAOYSA-N methyl 4-oxo-6-phenylmethoxy-1h-quinoline-2-carboxylate Chemical compound C1=CC2=NC(C(=O)OC)=CC(O)=C2C=C1OCC1=CC=CC=C1 ISEUSWBMFAUWGC-UHFFFAOYSA-N 0.000 description 1
• UERPMSGKRPJJSM-UHFFFAOYSA-N methyl 4-oxo-6-propan-2-yloxy-1h-quinoline-2-carboxylate Chemical compound C1=C(OC(C)C)C=CC2=NC(C(=O)OC)=CC(O)=C21 UERPMSGKRPJJSM-UHFFFAOYSA-N 0.000 description 1
• MWDJRMIHHQKFDX-UHFFFAOYSA-N methyl 4-oxo-7-(trifluoromethoxy)-1h-quinoline-2-carboxylate Chemical compound C1=CC(OC(F)(F)F)=CC2=NC(C(=O)OC)=CC(O)=C21 MWDJRMIHHQKFDX-UHFFFAOYSA-N 0.000 description 1
• HXMSYFTWUSYAPH-UHFFFAOYSA-N methyl 4-oxo-7-(trifluoromethyl)-1h-quinoline-2-carboxylate Chemical compound C1=CC(C(F)(F)F)=CC2=NC(C(=O)OC)=CC(O)=C21 HXMSYFTWUSYAPH-UHFFFAOYSA-N 0.000 description 1
• VLZYGTRQYVQNHJ-UHFFFAOYSA-N methyl 4-oxo-7-phenylmethoxy-1h-quinoline-2-carboxylate Chemical compound C=1C2=NC(C(=O)OC)=CC(O)=C2C=CC=1OCC1=CC=CC=C1 VLZYGTRQYVQNHJ-UHFFFAOYSA-N 0.000 description 1
• ZXHCYCLBSVNODY-UHFFFAOYSA-N methyl 4-oxo-7-propoxy-1h-quinoline-2-carboxylate Chemical compound OC1=CC(C(=O)OC)=NC2=CC(OCCC)=CC=C21 ZXHCYCLBSVNODY-UHFFFAOYSA-N 0.000 description 1
• DXSRVGHSPKNIAB-UHFFFAOYSA-N methyl 5-(4-ethoxy-4-oxobutoxy)-4-oxo-1h-quinoline-2-carboxylate Chemical compound COC(=O)C1=CC(O)=C2C(OCCCC(=O)OCC)=CC=CC2=N1 DXSRVGHSPKNIAB-UHFFFAOYSA-N 0.000 description 1
• LYBGSHMYWHJYRI-UHFFFAOYSA-N methyl 5-(diacetylamino)-4-oxo-1h-quinoline-2-carboxylate Chemical compound CC(=O)N(C(C)=O)C1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 LYBGSHMYWHJYRI-UHFFFAOYSA-N 0.000 description 1
• OFVIWZAPAWYJOU-UHFFFAOYSA-N methyl 5-(hydroxymethoxy)-4-oxo-1h-quinoline-2-carboxylate Chemical compound OCOC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 OFVIWZAPAWYJOU-UHFFFAOYSA-N 0.000 description 1
• OXTVUJAXIVALGT-UHFFFAOYSA-N methyl 5-acetamido-4-oxo-1h-quinoline-2-carboxylate Chemical compound CC(=O)NC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 OXTVUJAXIVALGT-UHFFFAOYSA-N 0.000 description 1
• USRGKPYANAVHOW-UHFFFAOYSA-N methyl 5-amino-4-oxo-1h-quinoline-2-carboxylate Chemical compound NC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 USRGKPYANAVHOW-UHFFFAOYSA-N 0.000 description 1
• UOFBKHDWDOWCBE-UHFFFAOYSA-N methyl 5-hydroxy-4-oxo-1h-quinoline-2-carboxylate Chemical compound OC1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 UOFBKHDWDOWCBE-UHFFFAOYSA-N 0.000 description 1
• ZOKUJNGBPSXUEN-UHFFFAOYSA-N methyl 5-nitro-4-oxo-1h-quinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=CC2=NC(C(=O)OC)=CC(O)=C21 ZOKUJNGBPSXUEN-UHFFFAOYSA-N 0.000 description 1
• IAOJNGHTHOBUPV-UHFFFAOYSA-N methyl 6,7-difluoro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(F)C(F)=CC2=NC(C(=O)OC)=CC(O)=C21 IAOJNGHTHOBUPV-UHFFFAOYSA-N 0.000 description 1
• SRRWUPWAZYFBKK-UHFFFAOYSA-N methyl 6-(diethylaminomethyl)-4-oxo-1h-quinoline-2-carboxylate Chemical compound N1=C(C(=O)OC)C=C(O)C2=CC(CN(CC)CC)=CC=C21 SRRWUPWAZYFBKK-UHFFFAOYSA-N 0.000 description 1
• POWMRSDSYBXKTH-UHFFFAOYSA-N methyl 6-(dimethylamino)-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(N(C)C)C=CC2=NC(C(=O)OC)=CC(O)=C21 POWMRSDSYBXKTH-UHFFFAOYSA-N 0.000 description 1
• QKMURGWSCDSNMN-UHFFFAOYSA-N methyl 6-acetyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound CC(=O)C1=CC=C2NC(C(=O)OC)=CC(=O)C2=C1 QKMURGWSCDSNMN-UHFFFAOYSA-N 0.000 description 1
• LTCKDZAUNSZESX-UHFFFAOYSA-N methyl 6-amino-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(N)C=CC2=NC(C(=O)OC)=CC(O)=C21 LTCKDZAUNSZESX-UHFFFAOYSA-N 0.000 description 1
• QULFUAQYCCSQAG-UHFFFAOYSA-N methyl 6-carbamoyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(C(N)=O)C=CC2=NC(C(=O)OC)=CC(O)=C21 QULFUAQYCCSQAG-UHFFFAOYSA-N 0.000 description 1
• HESVUOITGSAKKR-UHFFFAOYSA-N methyl 6-chloro-4-oxo-1h-quinoline-2-carboxylate Chemical compound ClC1=CC=C2NC(C(=O)OC)=CC(=O)C2=C1 HESVUOITGSAKKR-UHFFFAOYSA-N 0.000 description 1
• RVQKBOJONGSIDH-UHFFFAOYSA-N methyl 6-chloro-5-methyl-4-oxo-3h-quinoline-2-carboxylate Chemical compound C1=C(Cl)C(C)=C2C(=O)CC(C(=O)OC)=NC2=C1 RVQKBOJONGSIDH-UHFFFAOYSA-N 0.000 description 1
• IMSQMUNVQFYCPF-UHFFFAOYSA-N methyl 6-ethoxy-4-oxo-1h-quinoline-2-carboxylate Chemical compound N1=C(C(=O)OC)C=C(O)C2=CC(OCC)=CC=C21 IMSQMUNVQFYCPF-UHFFFAOYSA-N 0.000 description 1
• PBNYNLXOQRWFDR-UHFFFAOYSA-N methyl 6-ethyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound N1=C(C(=O)OC)C=C(O)C2=CC(CC)=CC=C21 PBNYNLXOQRWFDR-UHFFFAOYSA-N 0.000 description 1
• BESDSRIEDPEFRN-UHFFFAOYSA-N methyl 6-fluoro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(F)C=CC2=NC(C(=O)OC)=CC(O)=C21 BESDSRIEDPEFRN-UHFFFAOYSA-N 0.000 description 1
• KDMHMHBQWSJHSI-UHFFFAOYSA-N methyl 6-methoxy-4-oxo-1h-quinoline-2-carboxylate Chemical compound COC1=CC=C2NC(C(=O)OC)=CC(=O)C2=C1 KDMHMHBQWSJHSI-UHFFFAOYSA-N 0.000 description 1
• OFNPBZVQMSFLIS-UHFFFAOYSA-N methyl 6-nitro-4-oxo-1h-quinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)OC)=CC(=O)C2=C1 OFNPBZVQMSFLIS-UHFFFAOYSA-N 0.000 description 1
• BKSHXXHCHOZUDL-UHFFFAOYSA-N methyl 7-[2-(diethylamino)ethoxy]-4-oxo-1h-quinoline-2-carboxylate Chemical compound OC1=CC(C(=O)OC)=NC2=CC(OCCN(CC)CC)=CC=C21 BKSHXXHCHOZUDL-UHFFFAOYSA-N 0.000 description 1
• OKHLVOCPJRTOQQ-UHFFFAOYSA-N methyl 7-acetyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(C(C)=O)=CC2=NC(C(=O)OC)=CC(O)=C21 OKHLVOCPJRTOQQ-UHFFFAOYSA-N 0.000 description 1
• HNKLSMKAQAVMKQ-UHFFFAOYSA-N methyl 7-bromo-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(Br)=CC2=NC(C(=O)OC)=CC(O)=C21 HNKLSMKAQAVMKQ-UHFFFAOYSA-N 0.000 description 1
• QHPKUXTUEVUQAZ-UHFFFAOYSA-N methyl 7-chloro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(Cl)C=C2NC(C(=O)OC)=CC(=O)C2=C1 QHPKUXTUEVUQAZ-UHFFFAOYSA-N 0.000 description 1
• WFEYMCITSCYMSP-UHFFFAOYSA-N methyl 7-chloro-6-fluoro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(F)C(Cl)=CC2=NC(C(=O)OC)=CC(O)=C21 WFEYMCITSCYMSP-UHFFFAOYSA-N 0.000 description 1
• MPAAKJHSTVGSHE-UHFFFAOYSA-N methyl 7-chloro-6-methoxy-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(OC)C(Cl)=CC2=NC(C(=O)OC)=CC(O)=C21 MPAAKJHSTVGSHE-UHFFFAOYSA-N 0.000 description 1
• HSZVCJOLXPSIQI-UHFFFAOYSA-N methyl 7-chloro-6-methyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=C(C)C(Cl)=CC2=NC(C(=O)OC)=CC(O)=C21 HSZVCJOLXPSIQI-UHFFFAOYSA-N 0.000 description 1
• FJIHNTFXUYMFRI-UHFFFAOYSA-N methyl 7-cyano-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(C#N)=CC2=NC(C(=O)OC)=CC(O)=C21 FJIHNTFXUYMFRI-UHFFFAOYSA-N 0.000 description 1
• XGTZLBOMFGBSAL-UHFFFAOYSA-N methyl 7-ethyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound OC1=CC(C(=O)OC)=NC2=CC(CC)=CC=C21 XGTZLBOMFGBSAL-UHFFFAOYSA-N 0.000 description 1
• GWISOUSAPFLHLI-UHFFFAOYSA-N methyl 7-fluoro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(F)=CC2=NC(C(=O)OC)=CC(O)=C21 GWISOUSAPFLHLI-UHFFFAOYSA-N 0.000 description 1
• MUJXVVHLAUTTHP-UHFFFAOYSA-N methyl 7-methoxy-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC(OC)=CC2=NC(C(=O)OC)=CC(O)=C21 MUJXVVHLAUTTHP-UHFFFAOYSA-N 0.000 description 1
• DGNJPSYPDOPQQW-UHFFFAOYSA-N methyl 7-nitro-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC([N+]([O-])=O)=CC2=NC(C(=O)OC)=CC(O)=C21 DGNJPSYPDOPQQW-UHFFFAOYSA-N 0.000 description 1
• LXGWTGWGUFVSGH-UHFFFAOYSA-N methyl 8-methyl-4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC=C(C)C2=NC(C(=O)OC)=CC(O)=C21 LXGWTGWGUFVSGH-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
• 229920003087 methylethyl cellulose Polymers 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
• 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Chemical group 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 230000007505 plaque formation Effects 0.000 description 1
• 238000002616 plasmapheresis Methods 0.000 description 1
• 210000004623 platelet-rich plasma Anatomy 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 201000011461 pre-eclampsia Diseases 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000000473 propyl gallate Substances 0.000 description 1
• 235000010388 propyl gallate Nutrition 0.000 description 1
• 229940075579 propyl gallate Drugs 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000003331 prothrombotic effect Effects 0.000 description 1
• 210000001243 pseudopodia Anatomy 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000002278 reconstructive surgery Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 229910052717 sulfur Chemical group 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 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
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 230000002537 thrombolytic effect Effects 0.000 description 1
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
• 229960005001 ticlopidine Drugs 0.000 description 1
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940117013 triethanolamine oleate Drugs 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 230000003966 vascular damage Effects 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 108010047303 von Willebrand Factor Proteins 0.000 description 1
• 102100036537 von Willebrand factor Human genes 0.000 description 1
• 229960001134 von willebrand factor Drugs 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1