NO319816B1 - Nitrogenholdige heterocykler,anvendelse av disse for fremstilling av medikamenter samt farmasoytiske preparater. - Google Patents

Info

Publication number

NO319816B1

NO319816B1 NO20013072A NO20013072A NO319816B1 NO 319816 B1 NO319816 B1 NO 319816B1 NO 20013072 A NO20013072 A NO 20013072A NO 20013072 A NO20013072 A NO 20013072A NO 319816 B1 NO319816 B1 NO 319816B1

Authority

NO

Norway

Prior art keywords

biphen

methyl

methoxyphenyl

phenyl

aminobenzisoxazol

Prior art date

1998-12-23

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003814 drug Substances 0.000 title claims description 20
• 229940079593 drug Drugs 0.000 title claims description 8
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
• 238000004519 manufacturing process Methods 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims description 381
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 200
• -1 2-(aminosulfonyl)phenyl Chemical group 0.000 claims description 94
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 77
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 43
• 150000003839 salts Chemical class 0.000 claims description 35
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 23
• 125000004429 atom Chemical group 0.000 claims description 18
• 208000001435 Thromboembolism Diseases 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 125000004169 (C1-C6) alkyl 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
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 8
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
• 125000002883 imidazolyl group Chemical group 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 7
• 125000002837 carbocyclic group Chemical group 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
• XZMVYWXGZUMIFK-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one Chemical compound O=C1NCCC2=C1NN=C2 XZMVYWXGZUMIFK-UHFFFAOYSA-N 0.000 claims description 2
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 claims 1
• TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims 1
• 101150002896 RNR2 gene Proteins 0.000 claims 1
• 235000015278 beef Nutrition 0.000 claims 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• 125000001207 fluorophenyl group Chemical group 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 486
• 239000000243 solution Substances 0.000 description 286
• 235000019439 ethyl acetate Nutrition 0.000 description 198
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 184
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 172
• 229910001868 water Inorganic materials 0.000 description 171
• 239000011541 reaction mixture Substances 0.000 description 159
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 147
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 142
• 239000000203 mixture Substances 0.000 description 142
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 124
• 239000012267 brine Substances 0.000 description 116
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 116
• 239000003039 volatile agent Substances 0.000 description 112
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 97
• 239000007787 solid Substances 0.000 description 95
• 239000000047 product Substances 0.000 description 85
• 238000010992 reflux Methods 0.000 description 83
• 239000000460 chlorine Substances 0.000 description 78
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
• 238000005481 NMR spectroscopy Methods 0.000 description 75
• 238000000034 method Methods 0.000 description 71
• 239000000741 silica gel Substances 0.000 description 71
• 229910002027 silica gel Inorganic materials 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
• 230000002829 reductive effect Effects 0.000 description 61
• 238000003756 stirring Methods 0.000 description 60
• 238000000746 purification Methods 0.000 description 58
• 230000002441 reversible effect Effects 0.000 description 58
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 56
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
• 229920006395 saturated elastomer Polymers 0.000 description 45
• 235000002639 sodium chloride Nutrition 0.000 description 43
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 34
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 34
• 238000002953 preparative HPLC Methods 0.000 description 34
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
• 239000002904 solvent Substances 0.000 description 28
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
• 235000019341 magnesium sulphate Nutrition 0.000 description 27
• 229960000583 acetic acid Drugs 0.000 description 25
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 24
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 23
• 108010074860 Factor Xa Proteins 0.000 description 22
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
• 239000002253 acid Substances 0.000 description 22
• 238000010828 elution Methods 0.000 description 22
• 239000011734 sodium Substances 0.000 description 22
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 21
• 239000003112 inhibitor Substances 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• 238000004587 chromatography analysis Methods 0.000 description 20
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
• 239000004480 active ingredient Substances 0.000 description 19
• 239000003795 chemical substances by application Substances 0.000 description 19
• 239000007789 gas Substances 0.000 description 19
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• 229910000027 potassium carbonate Inorganic materials 0.000 description 18
• 238000003818 flash chromatography Methods 0.000 description 17
• 239000000651 prodrug Chemical group 0.000 description 17
• 229940002612 prodrug Drugs 0.000 description 17
• 239000000377 silicon dioxide Substances 0.000 description 17
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 17
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 16
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 16
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
• 108090000190 Thrombin Proteins 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000003480 eluent Substances 0.000 description 15
• 235000019253 formic acid Nutrition 0.000 description 15
• 239000011780 sodium chloride Substances 0.000 description 15
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• 125000002619 bicyclic group Chemical group 0.000 description 13
• 239000006260 foam Substances 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• 239000012044 organic layer Substances 0.000 description 13
• 229960004072 thrombin Drugs 0.000 description 13
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 12
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 12
• JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 11
• 125000000623 heterocyclic group Chemical group 0.000 description 11
• 238000004007 reversed phase HPLC Methods 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• DGUWACLYDSWXRZ-UHFFFAOYSA-N (2-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C=O DGUWACLYDSWXRZ-UHFFFAOYSA-N 0.000 description 10
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 239000002552 dosage form Substances 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 230000002401 inhibitory effect Effects 0.000 description 10
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
• 239000000758 substrate Substances 0.000 description 10
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 239000003146 anticoagulant agent Substances 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 150000004820 halides Chemical class 0.000 description 9
• 238000010438 heat treatment Methods 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 229940124597 therapeutic agent Drugs 0.000 description 9
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• 150000001540 azides Chemical class 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• 238000010926 purge Methods 0.000 description 8
• WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 7
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 7
• RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 7
• 229960001171 acetohydroxamic acid Drugs 0.000 description 7
• 229940127219 anticoagulant drug Drugs 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 238000004440 column chromatography Methods 0.000 description 7
• 150000002148 esters Chemical group 0.000 description 7
• 238000004108 freeze drying Methods 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 235000017281 sodium acetate Nutrition 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 7
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 6
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• 229940122388 Thrombin inhibitor Drugs 0.000 description 6
• 208000007536 Thrombosis Diseases 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 230000003197 catalytic effect Effects 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 229940088598 enzyme Drugs 0.000 description 6
• 238000002474 experimental method Methods 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 239000003527 fibrinolytic agent Substances 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• 229910052717 sulfur Inorganic materials 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 239000003868 thrombin inhibitor Substances 0.000 description 6
• 238000003828 vacuum filtration Methods 0.000 description 6
• PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 5
• BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 5
• SHRRRNSPESGSCM-UHFFFAOYSA-N 4-amino-1h-pyrazole-5-carboxylic acid Chemical compound NC1=CNN=C1C(O)=O SHRRRNSPESGSCM-UHFFFAOYSA-N 0.000 description 5
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 5
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 229940127218 antiplatelet drug Drugs 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 229910052796 boron Inorganic materials 0.000 description 5
• 238000009833 condensation Methods 0.000 description 5
• 230000005494 condensation Effects 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 235000019359 magnesium stearate Nutrition 0.000 description 5
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 229920000642 polymer Polymers 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 229940087562 sodium acetate trihydrate Drugs 0.000 description 5
• 239000012279 sodium borohydride Substances 0.000 description 5
• 229910000033 sodium borohydride Inorganic materials 0.000 description 5
• 235000010288 sodium nitrite Nutrition 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 5
• 238000010792 warming Methods 0.000 description 5
• JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 4
• VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 description 4
• AXINVSXSGNSVLV-UHFFFAOYSA-N 1h-pyrazol-4-amine Chemical compound NC=1C=NNC=1 AXINVSXSGNSVLV-UHFFFAOYSA-N 0.000 description 4
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 4
• 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 4
• DKDWFDPBBSXJOV-UHFFFAOYSA-N 4-acetyl-1-(4-bromophenyl)-5-hydroxy-2,3-dihydropyridin-6-one Chemical compound C1CC(C(=O)C)=C(O)C(=O)N1C1=CC=C(Br)C=C1 DKDWFDPBBSXJOV-UHFFFAOYSA-N 0.000 description 4
• DZPADZCQSQHOBT-UHFFFAOYSA-N 4-azido-5-cyano-2-(4-methoxyphenyl)pyrazole-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1N1C(C(O)=O)=C(N=[N+]=[N-])C(C#N)=N1 DZPADZCQSQHOBT-UHFFFAOYSA-N 0.000 description 4
• GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 4
• 229940123583 Factor Xa inhibitor Drugs 0.000 description 4
• 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 4
• 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 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• 238000002835 absorbance Methods 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 230000023555 blood coagulation Effects 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 239000003638 chemical reducing agent Substances 0.000 description 4
• 238000003776 cleavage reaction Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 125000004093 cyano group Chemical group *C#N 0.000 description 4
• 239000012954 diazonium Substances 0.000 description 4
• 210000001035 gastrointestinal tract Anatomy 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 150000002429 hydrazines Chemical class 0.000 description 4
• 150000002576 ketones Chemical group 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 229910000160 potassium phosphate Inorganic materials 0.000 description 4
• 235000011009 potassium phosphates Nutrition 0.000 description 4
• 230000007017 scission Effects 0.000 description 4
• 238000010898 silica gel chromatography Methods 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 235000017550 sodium carbonate Nutrition 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• 229960000103 thrombolytic agent Drugs 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 4
• 235000019798 tripotassium phosphate Nutrition 0.000 description 4
• 238000001665 trituration Methods 0.000 description 4
• FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 3
• GGZBDQZNMRKVJO-UHFFFAOYSA-N 1,4,6,7-tetrahydropyrazolo[4,3-b]pyridin-5-one Chemical class N1C(=O)CCC2=C1C=NN2 GGZBDQZNMRKVJO-UHFFFAOYSA-N 0.000 description 3
• RXAZQOZFHKFLLQ-UHFFFAOYSA-N 1-(4-bromophenyl)-6-morpholin-4-yl-3,4-dihydro-2h-azepin-7-one Chemical compound C1=CC(Br)=CC=C1N1C(=O)C(N2CCOCC2)=CCCC1 RXAZQOZFHKFLLQ-UHFFFAOYSA-N 0.000 description 3
• QLTFFFKOTZQZOG-UHFFFAOYSA-N 2-(3-cyano-4-fluorophenyl)-4-nitro-5-(trifluoromethyl)pyrazole-3-carboxylic acid Chemical compound OC(=O)C1=C([N+]([O-])=O)C(C(F)(F)F)=NN1C1=CC=C(F)C(C#N)=C1 QLTFFFKOTZQZOG-UHFFFAOYSA-N 0.000 description 3
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
• NVGVSTRNTCEDIK-UHFFFAOYSA-N 4-acetyl-1-(4-bromophenyl)piperidine-2,3-dione Chemical compound O=C1C(=O)C(C(=O)C)CCN1C1=CC=C(Br)C=C1 NVGVSTRNTCEDIK-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 102000007625 Hirudins Human genes 0.000 description 3
• 108010007267 Hirudins Proteins 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
• TUEIURIZJQRMQE-UHFFFAOYSA-N [2-(tert-butylsulfamoyl)phenyl]boronic acid Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=CC=C1B(O)O TUEIURIZJQRMQE-UHFFFAOYSA-N 0.000 description 3
• 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 3
• 229960001138 acetylsalicylic acid Drugs 0.000 description 3
• 238000005917 acylation reaction Methods 0.000 description 3
• 150000001336 alkenes Chemical class 0.000 description 3
• 150000004703 alkoxides Chemical class 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 3
• 239000004744 fabric Substances 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 229940093915 gynecological organic acid Drugs 0.000 description 3
• WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 3
• 229940006607 hirudin Drugs 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
• 125000000468 ketone group Chemical group 0.000 description 3
• 150000003951 lactams Chemical class 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 3
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000012047 saturated solution Substances 0.000 description 3
• 235000012239 silicon dioxide Nutrition 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 150000003457 sulfones Chemical group 0.000 description 3
• 125000004434 sulfur atom Chemical group 0.000 description 3
• 230000002195 synergetic effect Effects 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 230000002537 thrombolytic effect Effects 0.000 description 3
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 3
• 229960005356 urokinase Drugs 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• YIJGCAUGPCNCCN-UHFFFAOYSA-N 2-fluoro-5-hydrazinylbenzonitrile;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C(C#N)=C1 YIJGCAUGPCNCCN-UHFFFAOYSA-N 0.000 description 2
• LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
• GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 2
• ALWVPFIPTLPTEV-UHFFFAOYSA-N 2h-pyrazolo[4,3-d]pyrimidine-3,5-dione Chemical class C1=NC(=O)N=C2C(=O)NN=C21 ALWVPFIPTLPTEV-UHFFFAOYSA-N 0.000 description 2
• TTWKKIVHHLEIPT-UHFFFAOYSA-N 3-[6-(4-bromophenyl)-3-methyl-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-1-yl]benzonitrile Chemical compound CC1=NN(C=2C=C(C=CC=2)C#N)C(C2=O)=C1CCN2C1=CC=C(Br)C=C1 TTWKKIVHHLEIPT-UHFFFAOYSA-N 0.000 description 2
• SBOSIWQIJOMACM-UHFFFAOYSA-N 3-hydrazinylbenzonitrile Chemical compound NNC1=CC=CC(C#N)=C1 SBOSIWQIJOMACM-UHFFFAOYSA-N 0.000 description 2
• JOGQTRBQPHHOPW-UHFFFAOYSA-N 4-azido-5-cyano-2-(2-methylphenyl)pyrazole-3-carboxylic acid Chemical compound CC1=CC=CC=C1N1C(C(O)=O)=C(N=[N+]=[N-])C(C#N)=N1 JOGQTRBQPHHOPW-UHFFFAOYSA-N 0.000 description 2
• ALKTWONWCSOKPI-UHFFFAOYSA-N 4-azido-5-ethoxycarbonyl-2-(2-methylphenyl)pyrazole-3-carboxylic acid Chemical compound OC(=O)C1=C(N=[N+]=[N-])C(C(=O)OCC)=NN1C1=CC=CC=C1C ALKTWONWCSOKPI-UHFFFAOYSA-N 0.000 description 2
• FTLWWFVEHJPUDN-UHFFFAOYSA-N 4-azido-n-(4-bromophenyl)-5-cyano-2-(4-methoxyphenyl)pyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)NC=2C=CC(Br)=CC=2)=C(N=[N+]=[N-])C(C#N)=N1 FTLWWFVEHJPUDN-UHFFFAOYSA-N 0.000 description 2
• JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• XNUCLWXBKONXGO-UHFFFAOYSA-N 5-[6-(4-bromophenyl)-3-methyl-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-1-yl]-2-fluorobenzonitrile Chemical compound CC1=NN(C=2C=C(C(F)=CC=2)C#N)C(C2=O)=C1CCN2C1=CC=C(Br)C=C1 XNUCLWXBKONXGO-UHFFFAOYSA-N 0.000 description 2
• HHTRAISBAAXRKZ-UHFFFAOYSA-N 5-amino-2-fluorobenzonitrile Chemical compound NC1=CC=C(F)C(C#N)=C1 HHTRAISBAAXRKZ-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 108010058207 Anistreplase Proteins 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 2
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• 102000009123 Fibrin Human genes 0.000 description 2
• 108010073385 Fibrin Proteins 0.000 description 2
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 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 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 229930194542 Keto Natural products 0.000 description 2
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 229920000954 Polyglycolide Polymers 0.000 description 2
• XYONNSVDNIRXKZ-UHFFFAOYSA-N S-methyl methanethiosulfonate Chemical compound CSS(C)(=O)=O XYONNSVDNIRXKZ-UHFFFAOYSA-N 0.000 description 2
• 101150050048 SNCB gene Proteins 0.000 description 2
• 102000012479 Serine Proteases Human genes 0.000 description 2
• 108010022999 Serine Proteases Proteins 0.000 description 2
• 229910004298 SiO 2 Inorganic materials 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 206010047249 Venous thrombosis Diseases 0.000 description 2
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• 230000002776 aggregation Effects 0.000 description 2
• 238000004220 aggregation Methods 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• 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 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 235000011089 carbon dioxide Nutrition 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 150000007942 carboxylates Chemical class 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 230000015271 coagulation Effects 0.000 description 2
• 238000005345 coagulation Methods 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 239000007891 compressed tablet Substances 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000006193 diazotization reaction Methods 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
• 125000005594 diketone group Chemical group 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 150000002081 enamines Chemical class 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• 229950003499 fibrin Drugs 0.000 description 2
• 230000003480 fibrinolytic effect Effects 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 210000000936 intestine Anatomy 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 150000002513 isocyanates Chemical class 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• RHJKYMPLLLDJBM-UHFFFAOYSA-N methyl 4-amino-5-cyano-2-(2-methylphenyl)pyrazole-3-carboxylate Chemical compound COC(=O)C1=C(N)C(C#N)=NN1C1=CC=CC=C1C RHJKYMPLLLDJBM-UHFFFAOYSA-N 0.000 description 2
• BOMUSNRXEZKFQJ-UHFFFAOYSA-N methyl 4-azido-5-[(4-bromophenyl)carbamoyl]-1-(4-methoxyphenyl)pyrazole-3-carboxylate Chemical compound [N-]=[N+]=NC=1C(C(=O)OC)=NN(C=2C=CC(OC)=CC=2)C=1C(=O)NC1=CC=C(Br)C=C1 BOMUSNRXEZKFQJ-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
• QDFFFEWWDVWXFO-UHFFFAOYSA-N n-[(2-aminophenyl)methyl]-2,2,2-trifluoroacetamide Chemical compound NC1=CC=CC=C1CNC(=O)C(F)(F)F QDFFFEWWDVWXFO-UHFFFAOYSA-N 0.000 description 2
• JUGUTNYZONPMAF-UHFFFAOYSA-N n-[[2-[7-(4-bromophenyl)-8-oxo-3-(trifluoromethyl)-5,6-dihydro-4h-pyrazolo[3,4-c]azepin-1-yl]phenyl]methyl]-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C(=O)NCC1=CC=CC=C1N1C(C(=O)N(C=2C=CC(Br)=CC=2)CCC2)=C2C(C(F)(F)F)=N1 JUGUTNYZONPMAF-UHFFFAOYSA-N 0.000 description 2
• 229910017604 nitric acid Inorganic materials 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
• 239000003182 parenteral nutrition solution Substances 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 2
• 229960002702 piroxicam Drugs 0.000 description 2
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 2
• 229920000747 poly(lactic acid) Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000004633 polyglycolic acid Substances 0.000 description 2
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000028327 secretion Effects 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
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• 239000012064 sodium phosphate buffer Substances 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 235000011150 stannous chloride Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-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
• 229960003766 thrombin (human) Drugs 0.000 description 2
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 2
• 229960005001 ticlopidine Drugs 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
• 230000009466 transformation Effects 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
• XDIYNQZUNSSENW-UUBOPVPUSA-N (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[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• YDMBNDUHUNWWRP-VJBWXMMDSA-N (2s)-1-[(2r)-2-amino-3-phenylpropanoyl]-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]piperidine-2-carboxamide Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C1=CC=CC=C1 YDMBNDUHUNWWRP-VJBWXMMDSA-N 0.000 description 1
• RGGOWBBBHWTTRE-UHFFFAOYSA-N (4-bromophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Br)C=C1 RGGOWBBBHWTTRE-UHFFFAOYSA-N 0.000 description 1
• FQHCPFMTXFJZJS-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1 FQHCPFMTXFJZJS-UHFFFAOYSA-N 0.000 description 1
• KQJTXYQXRHCWKW-PJSBSAQXSA-N (4s)-4-[[(2s,3s)-2-benzamido-3-methylpentanoyl]amino]-5-[[2-[[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid;hydrochloride Chemical compound Cl.N([C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)C1=CC=CC=C1 KQJTXYQXRHCWKW-PJSBSAQXSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• WHZFVPDGHPJAFU-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1NCCc2cn[nH]c12 WHZFVPDGHPJAFU-UHFFFAOYSA-N 0.000 description 1
• NLSCMSUFXRSBPR-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)-3-hydroxypiperidin-2-one Chemical compound O=C1C(O)CCCN1C1=CC=C(Br)C=C1F NLSCMSUFXRSBPR-UHFFFAOYSA-N 0.000 description 1
• IFUGFWTXJJUWJC-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)-6-morpholin-4-yl-3,4-dihydro-2h-azepin-7-one Chemical compound FC1=CC(Br)=CC=C1N1C(=O)C(N2CCOCC2)=CCCC1 IFUGFWTXJJUWJC-UHFFFAOYSA-N 0.000 description 1
• PVXASNLFSPZQDI-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)-6-morpholin-4-yl-5-(2,2,2-trifluoroacetyl)-3,4-dihydro-2h-azepin-7-one Chemical compound FC1=CC(Br)=CC=C1N1C(=O)C(N2CCOCC2)=C(C(=O)C(F)(F)F)CCC1 PVXASNLFSPZQDI-UHFFFAOYSA-N 0.000 description 1
• AFQZPWNKHNBYLO-UHFFFAOYSA-N 1-(4-bromophenyl)-5-morpholin-4-yl-2,3-dihydropyridin-6-one Chemical compound C1=CC(Br)=CC=C1N1C(=O)C(N2CCOCC2)=CCC1 AFQZPWNKHNBYLO-UHFFFAOYSA-N 0.000 description 1
• IOKBUJGYGFVUCP-UHFFFAOYSA-N 1-(4-bromophenyl)-6-morpholin-4-yl-5-(2,2,2-trifluoroacetyl)-3,4-dihydro-2h-azepin-7-one Chemical compound O=C1N(C=2C=CC(Br)=CC=2)CCCC(C(=O)C(F)(F)F)=C1N1CCOCC1 IOKBUJGYGFVUCP-UHFFFAOYSA-N 0.000 description 1
• NUKIWSHDUPMAAR-UHFFFAOYSA-N 1-(4-bromophenyl)azepan-2-one Chemical compound C1=CC(Br)=CC=C1N1C(=O)CCCCC1 NUKIWSHDUPMAAR-UHFFFAOYSA-N 0.000 description 1
• XFWLEIAUYYEOKS-UHFFFAOYSA-N 1-(4-bromophenyl)azepane-2,4-dione Chemical compound C1=CC(Br)=CC=C1N1C(=O)CC(=O)CCC1 XFWLEIAUYYEOKS-UHFFFAOYSA-N 0.000 description 1
• WMCKGGCUGBEVMQ-UHFFFAOYSA-N 1-[1-(4-bromophenyl)-6-morpholin-4-yl-2,3,4,7-tetrahydroazepin-5-yl]-2,2,2-trifluoroethanone Chemical compound BrC1=CC=C(C=C1)N1CC(=C(CCC1)C(C(F)(F)F)=O)N1CCOCC1 WMCKGGCUGBEVMQ-UHFFFAOYSA-N 0.000 description 1
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
• WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 1
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
• OFERIRWCHSOJJT-UHFFFAOYSA-N 2-(3-chloropropyl)-2-methyl-1,3-dioxolane Chemical compound ClCCCC1(C)OCCO1 OFERIRWCHSOJJT-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• FJWFMZMFZHSZNH-UHFFFAOYSA-N 2-fluoro-5-[7-(2-fluoro-4-iodophenyl)-8-oxo-3-(trifluoromethyl)-6h-pyrazolo[3,4-c]azepin-1-yl]benzonitrile Chemical compound C1=C(C#N)C(F)=CC=C1N1C(C(=O)N(C=2C(=CC(I)=CC=2)F)CC=C2)=C2C(C(F)(F)F)=N1 FJWFMZMFZHSZNH-UHFFFAOYSA-N 0.000 description 1
• MGANJOUQFOPFNS-UHFFFAOYSA-N 2-fluoro-5-hydrazinylbenzonitrile Chemical compound NNC1=CC=C(F)C(C#N)=C1 MGANJOUQFOPFNS-UHFFFAOYSA-N 0.000 description 1
• GWJSQKNYHPYZRN-UHFFFAOYSA-N 2-methylpropane-2-sulfonamide Chemical compound CC(C)(C)S(N)(=O)=O GWJSQKNYHPYZRN-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• KZGYIXAEJGDLFW-UHFFFAOYSA-N 3-[6-(4-bromo-2-fluorophenyl)-7-oxo-3-(trifluoromethyl)-4,5-dihydropyrazolo[3,4-c]pyridin-1-yl]benzonitrile Chemical compound FC1=CC(Br)=CC=C1N1C(=O)C(N(N=C2C(F)(F)F)C=3C=C(C=CC=3)C#N)=C2CC1 KZGYIXAEJGDLFW-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
• OLRXCKFWRROJFZ-UHFFFAOYSA-N 3-hydrazinylbenzonitrile;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=CC(C#N)=C1 OLRXCKFWRROJFZ-UHFFFAOYSA-N 0.000 description 1
• XJXWLNFWEADKMB-UHFFFAOYSA-N 3-nitro-2-oxopropanoic acid Chemical compound OC(=O)C(=O)C[N+]([O-])=O XJXWLNFWEADKMB-UHFFFAOYSA-N 0.000 description 1
• LASMFAUXVLVABR-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1h-pyrazolo[3,4-c]azepin-8-one Chemical compound O=C1NCCCC2=C1NN=C2 LASMFAUXVLVABR-UHFFFAOYSA-N 0.000 description 1
• PPQAVYYFHRYAHQ-UHFFFAOYSA-N 4,7-dihydro-1h-pyrazolo[4,3-b]pyridine-5,6-dione Chemical class N1C(=O)C(=O)CC2=C1C=NN2 PPQAVYYFHRYAHQ-UHFFFAOYSA-N 0.000 description 1
• IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
• PFRCHUQJCNONBJ-UHFFFAOYSA-N 4-amino-3-ethyl-5-methyl-1-(2-methylphenyl)pyrazolidine-3,5-dicarboxylic acid Chemical compound OC(=O)C1(C)C(N)C(CC)(C(O)=O)NN1C1=CC=CC=C1C PFRCHUQJCNONBJ-UHFFFAOYSA-N 0.000 description 1
• ZAWAYTBUESDGPH-UHFFFAOYSA-N 4-amino-n-(4-bromophenyl)-5-cyano-2-(4-methoxyphenyl)pyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)NC=2C=CC(Br)=CC=2)=C(N)C(C#N)=N1 ZAWAYTBUESDGPH-UHFFFAOYSA-N 0.000 description 1
• HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 1
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
• CEGROXPMOLPOMK-UHFFFAOYSA-N 4-azido-5-ethoxycarbonyl-2-(4-methoxyphenyl)pyrazole-3-carboxylic acid Chemical compound OC(=O)C1=C(N=[N+]=[N-])C(C(=O)OCC)=NN1C1=CC=C(OC)C=C1 CEGROXPMOLPOMK-UHFFFAOYSA-N 0.000 description 1
• NQDIDFRVHVZODH-UHFFFAOYSA-N 4-azido-5-n-(4-bromo-2-fluorophenyl)-1-(4-methoxyphenyl)pyrazole-3,5-dicarboxamide Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)NC=2C(=CC(Br)=CC=2)F)=C(N=[N+]=[N-])C(C(N)=O)=N1 NQDIDFRVHVZODH-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• XORHNJQEWQGXCN-UHFFFAOYSA-N 4-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C=1C=NNC=1 XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• DPEGXKDKCGXLNJ-UHFFFAOYSA-N 5-[7-(4-bromophenyl)-8-oxo-3-(trifluoromethyl)-5,6-dihydro-4h-pyrazolo[3,4-c]azepin-1-yl]-2-fluorobenzonitrile Chemical compound C1=C(C#N)C(F)=CC=C1N1C(C(=O)N(C=2C=CC(Br)=CC=2)CCC2)=C2C(C(F)(F)F)=N1 DPEGXKDKCGXLNJ-UHFFFAOYSA-N 0.000 description 1
• JYLJOZLUJOUFAO-UHFFFAOYSA-N 6-(4-bromo-2-fluorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-4,5-dihydropyrazolo[3,4-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C(=CC(Br)=CC=3)F)=C2C(C(F)(F)F)=N1 JYLJOZLUJOUFAO-UHFFFAOYSA-N 0.000 description 1
• HBPVGJGBRWIVSX-UHFFFAOYSA-N 6-bromohexanoyl chloride Chemical compound ClC(=O)CCCCCBr HBPVGJGBRWIVSX-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 1
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• 206010002388 Angina unstable Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• ATQYDHHEBRDHKA-UHFFFAOYSA-N CC1=NN(C2=C1CCN(C2)C3=CC=C(C=C3)Br)C4=CC(=C(C=C4)F)C#N Chemical compound CC1=NN(C2=C1CCN(C2)C3=CC=C(C=C3)Br)C4=CC(=C(C=C4)F)C#N ATQYDHHEBRDHKA-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010008088 Cerebral artery embolism Diseases 0.000 description 1
• 206010008092 Cerebral artery thrombosis Diseases 0.000 description 1
• CSAJDKLFKLISIL-UHFFFAOYSA-N Cl.NNC1=CC=CC=C1CNC(=O)C(F)(F)F Chemical compound Cl.NNC1=CC=CC=C1CNC(=O)C(F)(F)F CSAJDKLFKLISIL-UHFFFAOYSA-N 0.000 description 1
• 206010011091 Coronary artery thrombosis Diseases 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
• 206010051055 Deep vein thrombosis Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 238000006228 Dieckmann condensation reaction Methods 0.000 description 1
• 206010014513 Embolism arterial Diseases 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 108010014172 Factor V Proteins 0.000 description 1
• 108010088842 Fibrinolysin Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 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
• 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
• 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 1
• 206010061218 Inflammation Diseases 0.000 description 1
• RZIAABRFQASVSW-UHFFFAOYSA-N Isoquinoline N-oxide Chemical compound C1=CC=CC2=C[N+]([O-])=CC=C21 RZIAABRFQASVSW-UHFFFAOYSA-N 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 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
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• 125000003047 N-acetyl group Chemical class 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• 238000007126 N-alkylation reaction Methods 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• UHVWOYMVKGGBTQ-UHFFFAOYSA-N N=1N=CC2=CC=CNC(C12)=O Chemical compound N=1N=CC2=CC=CNC(C12)=O UHVWOYMVKGGBTQ-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• XYTUTGCCBBCBSR-UHFFFAOYSA-N OCCCCCCBr.Cl Chemical compound OCCCCCCBr.Cl XYTUTGCCBBCBSR-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 229910020667 PBr3 Inorganic materials 0.000 description 1
• 239000008118 PEG 6000 Substances 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
• 108090000113 Plasma Kallikrein Proteins 0.000 description 1
• 102100034869 Plasma kallikrein Human genes 0.000 description 1
• 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
• 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
• 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 108010094028 Prothrombin Proteins 0.000 description 1
• 102100027378 Prothrombin Human genes 0.000 description 1
• 208000010378 Pulmonary Embolism Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 206010063544 Renal embolism Diseases 0.000 description 1
• 108010039286 S 2238 Proteins 0.000 description 1
• 206010059054 Shunt thrombosis Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 108010023197 Streptokinase Proteins 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
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000003938 Thromboxane Receptors Human genes 0.000 description 1
• 108090000300 Thromboxane Receptors Proteins 0.000 description 1
• 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 208000032109 Transient ischaemic attack Diseases 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
• CFEHYFPCSUYZBT-UHFFFAOYSA-N [Sn].NN Chemical compound [Sn].NN CFEHYFPCSUYZBT-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001409 amidines Chemical class 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 235000012501 ammonium carbonate Nutrition 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 229960000983 anistreplase Drugs 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000002429 anti-coagulating effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000000702 anti-platelet effect Effects 0.000 description 1
• 230000002785 anti-thrombosis Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000004019 antithrombin Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
• 229960003856 argatroban 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
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000005199 aryl carbonyloxy group Chemical group 0.000 description 1
• YEJAJYAHJQIWNU-UHFFFAOYSA-N azelastine hydrochloride Chemical compound Cl.C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 YEJAJYAHJQIWNU-UHFFFAOYSA-N 0.000 description 1
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
• IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
• UDLLFLQFQMACJB-UHFFFAOYSA-N azidomethylbenzene Chemical compound [N-]=[N+]=NCC1=CC=CC=C1 UDLLFLQFQMACJB-UHFFFAOYSA-N 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 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
• 229960004365 benzoic acid Drugs 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 108010031969 benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide Proteins 0.000 description 1
• 125000005512 benztetrazolyl group Chemical group 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 150000001649 bromium compounds Chemical group 0.000 description 1
• KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 235000011132 calcium sulphate Nutrition 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001733 carboxylic acid esters Chemical group 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 239000000919 ceramic Substances 0.000 description 1
• 229940106189 ceramide Drugs 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 229960004926 chlorobutanol Drugs 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
• 235000012000 cholesterol Nutrition 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 208000002528 coronary thrombosis Diseases 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 238000006352 cycloaddition reaction Methods 0.000 description 1
• XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 1
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• DHZYXWMZLAKTQV-UHFFFAOYSA-N diazepin-3-one Chemical compound O=C1C=CC=CN=N1 DHZYXWMZLAKTQV-UHFFFAOYSA-N 0.000 description 1
• 150000001989 diazonium salts Chemical class 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
• JTCLETOKTVXXPH-UHFFFAOYSA-L dichlorotin ethanol dihydrate Chemical compound O.O.CCO.Cl[Sn]Cl JTCLETOKTVXXPH-UHFFFAOYSA-L 0.000 description 1
• DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
• 229960001259 diclofenac Drugs 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• OEHFRZLKGRKFAS-UHFFFAOYSA-N droxicam Chemical compound C12=CC=CC=C2S(=O)(=O)N(C)C(C2=O)=C1OC(=O)N2C1=CC=CC=N1 OEHFRZLKGRKFAS-UHFFFAOYSA-N 0.000 description 1
• 229960001850 droxicam Drugs 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• OYQVQWIASIXXRT-UHFFFAOYSA-N ethyl 2,4-dioxopentanoate Chemical compound CCOC(=O)C(=O)CC(C)=O OYQVQWIASIXXRT-UHFFFAOYSA-N 0.000 description 1
• LINPNXVIAOSDBE-UHFFFAOYSA-N ethyl 4-acetyl-2-(4-methoxyphenyl)-5-(trifluoromethyl)pyrazole-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)=O)C(C(F)(F)F)=NN1C1=CC=C(OC)C=C1 LINPNXVIAOSDBE-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 229960000301 factor viii Drugs 0.000 description 1
• 210000001105 femoral artery Anatomy 0.000 description 1
• 210000003191 femoral vein Anatomy 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• KFIFDKLIFPYSAZ-UHFFFAOYSA-N formyloxy(phenyl)borinic acid Chemical compound O=COB(O)C1=CC=CC=C1 KFIFDKLIFPYSAZ-UHFFFAOYSA-N 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229960002989 glutamic acid Drugs 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000002366 halogen compounds Chemical class 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 150000002373 hemiacetals Chemical class 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• 231100000086 high toxicity Toxicity 0.000 description 1
• XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical class [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 150000002460 imidazoles Chemical class 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
• 201000010849 intracranial embolism Diseases 0.000 description 1
• 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 229940045996 isethionic acid Drugs 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• NVDGJIFJXLVCQU-UHFFFAOYSA-N isoquinolin-7-ylhydrazine Chemical compound C1=CN=CC2=CC(NN)=CC=C21 NVDGJIFJXLVCQU-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 229940040102 levulinic acid Drugs 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229940103185 mefenamate Drugs 0.000 description 1
• HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
• DMEKUKDWAIXWSL-UHFFFAOYSA-N n,n-dimethyl-7-nitro-9h-fluoren-2-amine Chemical compound [O-][N+](=O)C1=CC=C2C3=CC=C(N(C)C)C=C3CC2=C1 DMEKUKDWAIXWSL-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 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
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
• 230000000802 nitrating effect Effects 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229950006098 orthocaine Drugs 0.000 description 1
• 150000002905 orthoesters Chemical class 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
• QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 238000007248 oxidative elimination reaction Methods 0.000 description 1
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
• CNMOHEDUVVUVPP-UHFFFAOYSA-N piperidine-2,3-dione Chemical compound O=C1CCCNC1=O CNMOHEDUVVUVPP-UHFFFAOYSA-N 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
• 229940012957 plasmin Drugs 0.000 description 1
• 230000010118 platelet activation Effects 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011698 potassium fluoride Substances 0.000 description 1
• 235000003270 potassium fluoride Nutrition 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 229940039716 prothrombin Drugs 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 150000003217 pyrazoles Chemical class 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• LBFMENANQYHPPH-UHFFFAOYSA-N pyrazolo[3,4-c]pyridin-7-one Chemical compound O=C1N=CC=C2C=NN=C12 LBFMENANQYHPPH-UHFFFAOYSA-N 0.000 description 1
• DOTPSQVYOBAWPQ-UHFFFAOYSA-N pyrazolo[4,3-d]pyrimidin-3-one Chemical class N1=CN=C2C(=O)N=NC2=C1 DOTPSQVYOBAWPQ-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 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
• 238000011084 recovery Methods 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229910052702 rhenium Inorganic materials 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 108010073863 saruplase Proteins 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 150000003413 spiro compounds Chemical class 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000001119 stannous chloride Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 229960005202 streptokinase Drugs 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229950000244 sulfanilic acid Drugs 0.000 description 1
• MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 1
• 229960003329 sulfinpyrazone Drugs 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
• 229960000894 sulindac Drugs 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
• UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
• 201000005060 thrombophlebitis Diseases 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical group [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 201000010875 transient cerebral ischemia Diseases 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 108010036927 trypsin-like serine protease Proteins 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 230000007306 turnover Effects 0.000 description 1
• MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
• 235000012141 vanillin Nutrition 0.000 description 1
• FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
• 229960005080 warfarin Drugs 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1