RU2318807C2 - Пирролидин-2-оны в качестве ингибиторов фактора ха - Google Patents

Info

Publication number

RU2318807C2

RU2318807C2 RU2004122427/04A RU2004122427A RU2318807C2 RU 2318807 C2 RU2318807 C2 RU 2318807C2 RU 2004122427/04 A RU2004122427/04 A RU 2004122427/04A RU 2004122427 A RU2004122427 A RU 2004122427A RU 2318807 C2 RU2318807 C2 RU 2318807C2

Authority

RU

Russia

Prior art keywords

alkyl

oxopyrrolidin

found

mass spectrum

halogen

Prior art date

2001-12-21

Links

• Espacenet
• Global Dossier
• Discuss

• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 title claims abstract description 7
• 239000003112 inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 308
• -1 -(C2-C4)-alkenyl Chemical group 0.000 claims abstract description 137
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 88
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 73
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 65
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 60
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 58
• 125000003118 aryl group Chemical group 0.000 claims abstract description 41
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 40
• 150000003839 salts Chemical class 0.000 claims abstract description 39
• 239000012453 solvate Substances 0.000 claims abstract description 25
• 125000004450 alkenylene group Chemical group 0.000 claims abstract description 18
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 18
• 239000003814 drug Substances 0.000 claims abstract description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
• 125000004429 atom Chemical group 0.000 claims abstract description 4
• 125000005843 halogen group Chemical group 0.000 claims abstract 10
• 125000000217 alkyl group Chemical group 0.000 claims description 183
• 150000002367 halogens Chemical class 0.000 claims description 95
• 229910052736 halogen Inorganic materials 0.000 claims description 90
• 238000000034 method Methods 0.000 claims description 76
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 239000001257 hydrogen Substances 0.000 claims description 63
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 42
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 125000003342 alkenyl group Chemical group 0.000 claims description 23
• 229940123583 Factor Xa inhibitor Drugs 0.000 claims description 19
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 19
• 108010074860 Factor Xa Proteins 0.000 claims description 13
• 229940079593 drug Drugs 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 79
• 239000000126 substance Substances 0.000 abstract description 31
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 22
• 125000000623 heterocyclic group Chemical group 0.000 abstract description 7
• 230000000694 effects Effects 0.000 abstract description 3
• 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
• 229910003827 NRaRb Inorganic materials 0.000 abstract 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
• 230000007721 medicinal effect Effects 0.000 abstract 1
• 125000004434 sulfur atom Chemical group 0.000 abstract 1
• 238000001819 mass spectrum Methods 0.000 description 277
• 239000000543 intermediate Substances 0.000 description 266
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
• 238000004128 high performance liquid chromatography Methods 0.000 description 155
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
• 239000000243 solution Substances 0.000 description 127
• 239000000203 mixture Substances 0.000 description 88
• 230000002829 reductive effect Effects 0.000 description 86
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
• 239000011541 reaction mixture Substances 0.000 description 63
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 51
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 50
• 230000015572 biosynthetic process Effects 0.000 description 47
• 239000000741 silica gel Substances 0.000 description 47
• 229910002027 silica gel Inorganic materials 0.000 description 47
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 46
• 238000003786 synthesis reaction Methods 0.000 description 46
• 239000007787 solid Substances 0.000 description 45
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 40
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 38
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 28
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
• 239000002904 solvent Substances 0.000 description 27
• 235000019341 magnesium sulphate Nutrition 0.000 description 26
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
• 238000013459 approach Methods 0.000 description 23
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
• 239000012299 nitrogen atmosphere Substances 0.000 description 20
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 19
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 19
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 18
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• 230000002209 hydrophobic effect Effects 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• 235000019198 oils Nutrition 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• 238000006243 chemical reaction Methods 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
• 125000006239 protecting group Chemical group 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 14
• 239000000843 powder Substances 0.000 description 14
• 239000002585 base Substances 0.000 description 13
• 238000011282 treatment Methods 0.000 description 13
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 12
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
• 238000010828 elution Methods 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• 229910000029 sodium carbonate Inorganic materials 0.000 description 12
• 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 12
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 11
• 238000004587 chromatography analysis Methods 0.000 description 11
• 239000012043 crude product Substances 0.000 description 11
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 239000006260 foam Substances 0.000 description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 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 10
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 229910021529 ammonia Inorganic materials 0.000 description 9
• 230000002792 vascular Effects 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
• 238000002560 therapeutic procedure Methods 0.000 description 8
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 7
• 208000007536 Thrombosis Diseases 0.000 description 7
• 230000001154 acute effect Effects 0.000 description 7
• 239000003146 anticoagulant agent Substances 0.000 description 7
• 210000004369 blood Anatomy 0.000 description 7
• 239000008280 blood Substances 0.000 description 7
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 229910004298 SiO 2 Inorganic materials 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 230000009471 action Effects 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 150000004820 halides Chemical class 0.000 description 6
• 229910052751 metal Inorganic materials 0.000 description 6
• 239000002184 metal Substances 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 5
• IYFIYGSJZIICOZ-UHFFFAOYSA-N 6-chloronaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=CC(Cl)=CC=C21 IYFIYGSJZIICOZ-UHFFFAOYSA-N 0.000 description 5
• 206010002388 Angina unstable Diseases 0.000 description 5
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
• 208000005189 Embolism Diseases 0.000 description 5
• 108090000190 Thrombin Proteins 0.000 description 5
• 108010000499 Thromboplastin Proteins 0.000 description 5
• 102000002262 Thromboplastin Human genes 0.000 description 5
• 208000007814 Unstable Angina Diseases 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
• 238000006555 catalytic reaction Methods 0.000 description 5
• HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
• 230000015271 coagulation Effects 0.000 description 5
• 238000005345 coagulation Methods 0.000 description 5
• 235000019441 ethanol Nutrition 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 5
• 230000013011 mating Effects 0.000 description 5
• 235000011056 potassium acetate Nutrition 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 5
• 229960004072 thrombin Drugs 0.000 description 5
• 230000002537 thrombolytic effect Effects 0.000 description 5
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• 206010003658 Atrial Fibrillation Diseases 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
• 206010051055 Deep vein thrombosis Diseases 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102000009123 Fibrin Human genes 0.000 description 4
• 108010073385 Fibrin Proteins 0.000 description 4
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
• 108010094028 Prothrombin Proteins 0.000 description 4
• 102100027378 Prothrombin Human genes 0.000 description 4
• 208000010378 Pulmonary Embolism Diseases 0.000 description 4
• 206010047249 Venous thrombosis Diseases 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 229910002091 carbon monoxide Inorganic materials 0.000 description 4
• 239000006184 cosolvent Substances 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 238000000105 evaporative light scattering detection Methods 0.000 description 4
• 229950003499 fibrin Drugs 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
• 208000010125 myocardial infarction Diseases 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 238000002953 preparative HPLC Methods 0.000 description 4
• 229940039716 prothrombin Drugs 0.000 description 4
• 239000011347 resin Substances 0.000 description 4
• 229920005989 resin Polymers 0.000 description 4
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
• 229940124530 sulfonamide Drugs 0.000 description 4
• 230000009424 thromboembolic effect Effects 0.000 description 4
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 3
• ULMGZTXURRFXKU-AWEZNQCLSA-N (3s)-3-amino-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]pyrrolidin-2-one Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](N)CC1 ULMGZTXURRFXKU-AWEZNQCLSA-N 0.000 description 3
• JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 3
• DBRHLSDKJZQWQS-SFHVURJKSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-iodophenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound FC1=CC(I)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 DBRHLSDKJZQWQS-SFHVURJKSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
• 208000001435 Thromboembolism Diseases 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000908 ammonium hydroxide Substances 0.000 description 3
• 210000001367 artery Anatomy 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 3
• 150000001793 charged compounds Chemical class 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 150000001879 copper Chemical class 0.000 description 3
• 238000007887 coronary angioplasty Methods 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
• 239000003527 fibrinolytic agent Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• CYYZOBBSBUVOTI-SFHVURJKSA-N n-[(3s)-1-(4-bromo-2-fluorophenyl)-2-oxopyrrolidin-3-yl]-6-chloronaphthalene-2-sulfonamide Chemical compound FC1=CC(Br)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 CYYZOBBSBUVOTI-SFHVURJKSA-N 0.000 description 3
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
• DWJMBQYORXLGAE-UHFFFAOYSA-N pyridine-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=N1 DWJMBQYORXLGAE-UHFFFAOYSA-N 0.000 description 3
• 208000037803 restenosis Diseases 0.000 description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• BFUUSTKCHFKXMA-NSHDSACASA-N tert-butyl n-[(3s)-1-(2-fluoro-4-iodophenyl)-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(I)C=C1F BFUUSTKCHFKXMA-NSHDSACASA-N 0.000 description 3
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 229960000103 thrombolytic agent Drugs 0.000 description 3
• 230000001052 transient effect Effects 0.000 description 3
• 208000019553 vascular disease Diseases 0.000 description 3
• 210000005166 vasculature Anatomy 0.000 description 3
• VXVNAGROCBZNRD-UHFFFAOYSA-N (3-chloropyridin-4-yl)boronic acid;pentahydrate Chemical compound O.O.O.O.O.OB(O)C1=CC=NC=C1Cl VXVNAGROCBZNRD-UHFFFAOYSA-N 0.000 description 2
• XQJDSWCMNFJKNL-QRPNPIFTSA-N (3s)-3-amino-1-(2-fluoro-4-iodophenyl)pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(I)C=C1F XQJDSWCMNFJKNL-QRPNPIFTSA-N 0.000 description 2
• DMLOURXNMBCPCH-NSHDSACASA-N (3s)-3-amino-1-[4-(dimethylamino)phenyl]pyrrolidin-2-one Chemical compound C1=CC(N(C)C)=CC=C1N1C(=O)[C@@H](N)CC1 DMLOURXNMBCPCH-NSHDSACASA-N 0.000 description 2
• HPBAFJOZZYBLQN-ZOWNYOTGSA-N (3s)-3-amino-1-[5-(2-methylsulfonylphenyl)pyridin-2-yl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 HPBAFJOZZYBLQN-ZOWNYOTGSA-N 0.000 description 2
• YROOZFJECWVSFR-SHKUGAOPSA-N (e)-2-(5-chlorothiophen-2-yl)-n-[(3s)-1-[2-fluoro-4-(1-hydroxyethyl)phenyl]-2-oxopyrrolidin-3-yl]ethenesulfonamide Chemical compound FC1=CC(C(O)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)\C=C\C=2SC(Cl)=CC=2)CC1 YROOZFJECWVSFR-SHKUGAOPSA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• HJRUFJKWRVTNDE-UHFFFAOYSA-N 2-methyl-6-phenylbenzenesulfonamide Chemical compound C1(=CC=CC=C1)C1=C(C(=CC=C1)C)S(=O)(=O)N HJRUFJKWRVTNDE-UHFFFAOYSA-N 0.000 description 2
• LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 description 2
• 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 2
• IUPLTPUQZVHRKU-VMSUTVGLSA-N 4-[(3s)-3-[(2-amino-2-oxoethyl)-[(e)-2-(5-chlorothiophen-2-yl)ethenyl]sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluoro-n,n-dimethylbenzamide Chemical compound FC1=CC(C(=O)N(C)C)=CC=C1N1C(=O)[C@@H](N(CC(N)=O)S(=O)(=O)\C=C\C=2SC(Cl)=CC=2)CC1 IUPLTPUQZVHRKU-VMSUTVGLSA-N 0.000 description 2
• IWCRFKQOSXDKKV-VFADXPBXSA-N 4-[(3s)-3-[(2-amino-2-oxoethyl)-[(e)-2-(5-chlorothiophen-2-yl)ethenyl]sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluorobenzamide Chemical compound C([C@@H](C1=O)N(CC(=O)N)S(=O)(=O)\C=C\C=2SC(Cl)=CC=2)CN1C1=CC=C(C(N)=O)C=C1F IWCRFKQOSXDKKV-VFADXPBXSA-N 0.000 description 2
• QWSPOKCEAQQIPA-INIZCTEOSA-N 4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluoro-n,n-dimethylbenzamide Chemical compound FC1=CC(C(=O)N(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 QWSPOKCEAQQIPA-INIZCTEOSA-N 0.000 description 2
• OICQLLSBOAVDEG-SFHVURJKSA-N 4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluoro-n-methyl-n-propan-2-ylbenzamide Chemical compound FC1=CC(C(=O)N(C)C(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 OICQLLSBOAVDEG-SFHVURJKSA-N 0.000 description 2
• UFGRZHAPODFPFK-LBPRGKRZSA-N 5-(5-chlorothiophen-2-yl)-n-[(3s)-1-(2-fluoro-4-iodophenyl)-2-oxopyrrolidin-3-yl]thiophene-2-sulfonamide Chemical compound FC1=CC(I)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC(=CC=2)C=2SC(Cl)=CC=2)CC1 UFGRZHAPODFPFK-LBPRGKRZSA-N 0.000 description 2
• PVERUQSBHXPDNT-LBPRGKRZSA-N 5-(5-chlorothiophen-2-yl)-n-[(3s)-1-(2-fluoro-4-nitrophenyl)-2-oxopyrrolidin-3-yl]thiophene-2-sulfonamide Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC(=CC=2)C=2SC(Cl)=CC=2)CC1 PVERUQSBHXPDNT-LBPRGKRZSA-N 0.000 description 2
• RPEBFLBSZDYQHK-FQEVSTJZSA-N 5-chloro-n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]-1-benzofuran-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2OC3=CC=C(Cl)C=C3C=2)CC1 RPEBFLBSZDYQHK-FQEVSTJZSA-N 0.000 description 2
• URYUGIXRRMLQDX-FQEVSTJZSA-N 5-chloro-n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC=C(Cl)C=C3C=2)CC1 URYUGIXRRMLQDX-FQEVSTJZSA-N 0.000 description 2
• AROPCWWOJWOLSR-IBGZPJMESA-N 5-chloro-n-[(3s)-1-[5-(2-methylsulfonylphenyl)pyridin-2-yl]-2-oxopyrrolidin-3-yl]-1-benzofuran-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=CC=C(N2C([C@@H](NS(=O)(=O)C=3OC4=CC=C(Cl)C=C4C=3)CC2)=O)N=C1 AROPCWWOJWOLSR-IBGZPJMESA-N 0.000 description 2
• BJAQAGQVZPAQQO-CQSZACIVSA-N 6-chloro-n-[(3r)-1-(2-fluoro-4-nitrophenyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1C(=O)[C@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 BJAQAGQVZPAQQO-CQSZACIVSA-N 0.000 description 2
• WLWKOVDQSCYFIT-SFHVURJKSA-N 6-chloro-n-[(3s)-1-(2,4-dichlorophenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound ClC1=CC(Cl)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 WLWKOVDQSCYFIT-SFHVURJKSA-N 0.000 description 2
• FFTYFMHAVJGRLT-AWEZNQCLSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-iodophenyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound FC1=CC(I)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 FFTYFMHAVJGRLT-AWEZNQCLSA-N 0.000 description 2
• ILGUTMWZAPDUFC-NRFANRHFSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-pyrazol-1-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1N1C=CC=N1 ILGUTMWZAPDUFC-NRFANRHFSA-N 0.000 description 2
• JHSDONNXLGECJP-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-pyridin-3-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CC=CN=C1 JHSDONNXLGECJP-QHCPKHFHSA-N 0.000 description 2
• JARTVXTXEHGVLK-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-pyridin-4-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CC=NC=C1 JARTVXTXEHGVLK-QHCPKHFHSA-N 0.000 description 2
• CUDJWBCHLSJILY-NRFANRHFSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-pyrimidin-2-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=NC=CC=N1 CUDJWBCHLSJILY-NRFANRHFSA-N 0.000 description 2
• PTKJARGJBZKKBG-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-(2-fluoro-4-pyrimidin-5-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CN=CN=C1 PTKJARGJBZKKBG-QFIPXVFZSA-N 0.000 description 2
• MKPITSXLSYUZTL-SFHVURJKSA-N 6-chloro-n-[(3s)-1-(2-fluorophenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound FC1=CC=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 MKPITSXLSYUZTL-SFHVURJKSA-N 0.000 description 2
• ZWYKSXKEJZSBSW-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound FC1=CC(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)=CC=C1N1CCOCC1 ZWYKSXKEJZSBSW-QFIPXVFZSA-N 0.000 description 2
• JJPZFZVEAYFUIG-HNNXBMFYSA-N 6-chloro-n-[(3s)-1-(4-cyano-2-fluorophenyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound FC1=CC(C#N)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 JJPZFZVEAYFUIG-HNNXBMFYSA-N 0.000 description 2
• WXJFYWVEBPDPFE-FQEVSTJZSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]-1-benzofuran-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2OC3=CC(Cl)=CC=C3C=2)CC1 WXJFYWVEBPDPFE-FQEVSTJZSA-N 0.000 description 2
• IWLYDCWYPIQTKM-FQEVSTJZSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 IWLYDCWYPIQTKM-FQEVSTJZSA-N 0.000 description 2
• CADWTJXIMYKCPI-DEOSSOPVSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 CADWTJXIMYKCPI-DEOSSOPVSA-N 0.000 description 2
• QWAFXCXUGFXGSU-IBGZPJMESA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 QWAFXCXUGFXGSU-IBGZPJMESA-N 0.000 description 2
• FDQKHOISMOZZOM-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(4-methoxypyridin-3-yl)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound COC1=CC=NC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 FDQKHOISMOZZOM-QHCPKHFHSA-N 0.000 description 2
• NQCWYYRMBZXJGX-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(4-methylimidazol-1-yl)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=NC(C)=CN1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 NQCWYYRMBZXJGX-QFIPXVFZSA-N 0.000 description 2
• NEJMMVBQXXIZLM-SANMLTNESA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(4-propylpyridin-3-yl)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound CCCC1=CC=NC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 NEJMMVBQXXIZLM-SANMLTNESA-N 0.000 description 2
• HQNGCAGBPNUVMW-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=NC(OC)=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 HQNGCAGBPNUVMW-QHCPKHFHSA-N 0.000 description 2
• RXDHMZNMCQBOCI-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-[4-(2,4-dimethoxypyrimidin-5-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound COC1=NC(OC)=NC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 RXDHMZNMCQBOCI-QFIPXVFZSA-N 0.000 description 2
• XEPPBGIFWIHIMC-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-[4-(2-chloropyridin-3-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CC=CN=C1Cl XEPPBGIFWIHIMC-QFIPXVFZSA-N 0.000 description 2
• PEINEPXBFLVFAH-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-[4-(2-cyanopyridin-3-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CC=CN=C1C#N PEINEPXBFLVFAH-QHCPKHFHSA-N 0.000 description 2
• YBDJZXFQSJHDAK-QFIPXVFZSA-N 6-chloro-n-[(3s)-1-[4-(3-chloropyridin-2-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=NC=CC=C1Cl YBDJZXFQSJHDAK-QFIPXVFZSA-N 0.000 description 2
• GPRBXSLDGMVMHE-QHCPKHFHSA-N 6-chloro-n-[(3s)-1-[4-(3-chloropyridin-4-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CC=NC=C1Cl GPRBXSLDGMVMHE-QHCPKHFHSA-N 0.000 description 2
• HLOUITYXKMQLKP-NRFANRHFSA-N 6-chloro-n-[(3s)-1-[4-(dimethylamino)phenyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=CC(N(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 HLOUITYXKMQLKP-NRFANRHFSA-N 0.000 description 2
• ZXUSPRMZONAVAE-FYZYNONXSA-N 6-chloro-n-[(3s)-1-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;formic acid Chemical compound OC=O.CN(C)CC1=NC=CN1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 ZXUSPRMZONAVAE-FYZYNONXSA-N 0.000 description 2
• UXEMCPVJFZIQLY-HNNXBMFYSA-N 6-chloro-n-[(3s)-2-oxo-1-(1,3-thiazol-2-yl)pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)Cl)CN1C1=NC=CS1 UXEMCPVJFZIQLY-HNNXBMFYSA-N 0.000 description 2
• BJIDMLCNZZKMIH-QHCPKHFHSA-N 6-chloro-n-[(3s)-2-oxo-1-(5-phenylpyridin-2-yl)pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)Cl)CN1C(N=C1)=CC=C1C1=CC=CC=C1 BJIDMLCNZZKMIH-QHCPKHFHSA-N 0.000 description 2
• OJIGIZZLHVVHDI-LBPRGKRZSA-N 6-chloro-n-[(3s)-2-oxo-1-pyrazin-2-ylpyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3S2)Cl)CN1C1=CN=CC=N1 OJIGIZZLHVVHDI-LBPRGKRZSA-N 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 238000006418 Brown reaction Methods 0.000 description 2
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
• 0 Cc1cc(C=C*(C=C2)N)c2[n]1 Chemical compound Cc1cc(C=C*(C=C2)N)c2[n]1 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 206010011091 Coronary artery thrombosis Diseases 0.000 description 2
• 241000400611 Eucalyptus deanei Species 0.000 description 2
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
• 108010049003 Fibrinogen Proteins 0.000 description 2
• 102000008946 Fibrinogen Human genes 0.000 description 2
• 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 2
• 239000002841 Lewis acid Substances 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 229940127219 anticoagulant drug Drugs 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 125000005604 azodicarboxylate group Chemical group 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
• 229940092714 benzenesulfonic acid Drugs 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 208000002528 coronary thrombosis Diseases 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• 229940012952 fibrinogen Drugs 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 238000005342 ion exchange Methods 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 150000007517 lewis acids Chemical class 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• HRLPDILAYHUIIF-UHFFFAOYSA-N n-(2-bromophenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1Br HRLPDILAYHUIIF-UHFFFAOYSA-N 0.000 description 2
• OMWPMLGFYBTUAI-QFIPXVFZSA-N n-[(3s)-1-(4-tert-butylphenyl)-2-oxopyrrolidin-3-yl]-6-chloronaphthalene-2-sulfonamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1 OMWPMLGFYBTUAI-QFIPXVFZSA-N 0.000 description 2
• XSYKIZLRNJWRHS-QFIPXVFZSA-N n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]isoquinoline-5-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C3=CC=NC=C3C=CC=2)CC1 XSYKIZLRNJWRHS-QFIPXVFZSA-N 0.000 description 2
• DNKVPIZPJANMOI-NRFANRHFSA-N n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]quinoline-8-sulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)CC1 DNKVPIZPJANMOI-NRFANRHFSA-N 0.000 description 2
• IAMWCEASDIBIHV-QHCPKHFHSA-N n-[(3s)-1-[4-(5-bromopyridin-3-yl)-2-fluorophenyl]-2-oxopyrrolidin-3-yl]-6-chloronaphthalene-2-sulfonamide Chemical compound C=1C=C(N2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(Cl)=CC4=CC=3)CC2)=O)C(F)=CC=1C1=CN=CC(Br)=C1 IAMWCEASDIBIHV-QHCPKHFHSA-N 0.000 description 2
• AHPDMBNXVPMNIZ-VWLOTQADSA-N n-[(3s)-1-[4-[3-(aminomethyl)phenyl]-2-fluorophenyl]-2-oxopyrrolidin-3-yl]-6-chloronaphthalene-2-sulfonamide Chemical compound NCC1=CC=CC(C=2C=C(F)C(N3C([C@@H](NS(=O)(=O)C=4C=C5C=CC(Cl)=CC5=CC=4)CC3)=O)=CC=2)=C1 AHPDMBNXVPMNIZ-VWLOTQADSA-N 0.000 description 2
• RVBUCPJSOGYKLL-KRWDZBQOSA-N n-[4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluorophenyl]-2-methylpropanamide Chemical compound FC1=CC(NC(=O)C(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 RVBUCPJSOGYKLL-KRWDZBQOSA-N 0.000 description 2
• LWCWTOGPFHODIC-SFHVURJKSA-N n-[4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluorophenyl]-n-propan-2-ylformamide Chemical compound FC1=CC(N(C=O)C(C)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 LWCWTOGPFHODIC-SFHVURJKSA-N 0.000 description 2
• NDDFCISJARQACA-INIZCTEOSA-N n-[4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluorophenyl]acetamide Chemical compound FC1=CC(NC(=O)C)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 NDDFCISJARQACA-INIZCTEOSA-N 0.000 description 2
• GCHDBCRREDFLNE-INIZCTEOSA-N n-[4-[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-3-fluorophenyl]propanamide Chemical compound FC1=CC(NC(=O)CC)=CC=C1N1C(=O)[C@@H](NS(=O)(=O)C=2SC3=CC(Cl)=CC=C3C=2)CC1 GCHDBCRREDFLNE-INIZCTEOSA-N 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 229960003966 nicotinamide Drugs 0.000 description 2
• 235000005152 nicotinamide Nutrition 0.000 description 2
• 239000011570 nicotinamide Substances 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
• 239000003208 petroleum Substances 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 235000011007 phosphoric acid Nutrition 0.000 description 2
• 150000003016 phosphoric acids Chemical class 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 229910000160 potassium phosphate Inorganic materials 0.000 description 2
• 235000011009 potassium phosphates Nutrition 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• YKRLMZKCVQTOAZ-UHFFFAOYSA-N prop-1-ene-1-sulfonamide Chemical compound CC=CS(N)(=O)=O YKRLMZKCVQTOAZ-UHFFFAOYSA-N 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 235000010265 sodium sulphite Nutrition 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 2
• 229910000080 stannane Inorganic materials 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• SAZKBFGWWZNUEK-NSHDSACASA-N tert-butyl n-[(3s)-1-(4-amino-2-fluorophenyl)-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1F SAZKBFGWWZNUEK-NSHDSACASA-N 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• ZMBIFIMYKYMAES-UHFFFAOYSA-N (2-methylpropan-2-yl)oxycarbonyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)OC(=O)CBr ZMBIFIMYKYMAES-UHFFFAOYSA-N 0.000 description 1
• WDGWHKRJEBENCE-UHFFFAOYSA-N (3-carbamoylphenyl)boronic acid Chemical compound NC(=O)C1=CC=CC(B(O)O)=C1 WDGWHKRJEBENCE-UHFFFAOYSA-N 0.000 description 1
• VZTASVKZMHWCKC-ILKKLZGPSA-N (3S)-3-amino-1-pyrazin-2-ylpyrrolidin-2-one dihydrochloride Chemical compound Cl.Cl.N[C@H]1CCN(C1=O)c1cnccn1 VZTASVKZMHWCKC-ILKKLZGPSA-N 0.000 description 1
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
• URRAWKYQEHWWGQ-PPHPATTJSA-N (3s)-1-(4-acetyl-2-fluorophenyl)-3-aminopyrrolidin-2-one;hydrochloride Chemical compound Cl.FC1=CC(C(=O)C)=CC=C1N1C(=O)[C@@H](N)CC1 URRAWKYQEHWWGQ-PPHPATTJSA-N 0.000 description 1
• GRIMGJIIZAHMHJ-FVGYRXGTSA-N (3s)-1-(5-acetylpyridin-2-yl)-3-aminopyrrolidin-2-one;hydrochloride Chemical compound Cl.N1=CC(C(=O)C)=CC=C1N1C(=O)[C@@H](N)CC1 GRIMGJIIZAHMHJ-FVGYRXGTSA-N 0.000 description 1
• UYLFZMXVXSVULE-NSHDSACASA-N (3s)-3-amino-1-(2-fluoro-4-imidazol-1-ylphenyl)pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1C1=CC=C(N2C=NC=C2)C=C1F UYLFZMXVXSVULE-NSHDSACASA-N 0.000 description 1
• SNLZVXASQHQTBY-QRPNPIFTSA-N (3s)-3-amino-1-(2-fluoro-4-nitrophenyl)pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C([N+]([O-])=O)C=C1F SNLZVXASQHQTBY-QRPNPIFTSA-N 0.000 description 1
• CACRZEPOBVYAHY-NSHDSACASA-N (3s)-3-amino-1-(2-fluoro-4-prop-1-en-2-ylphenyl)pyrrolidin-2-one Chemical compound FC1=CC(C(=C)C)=CC=C1N1C(=O)[C@@H](N)CC1 CACRZEPOBVYAHY-NSHDSACASA-N 0.000 description 1
• AIYDLANGWZEMCT-LBPRGKRZSA-N (3s)-3-amino-1-(3-fluoro-4-morpholin-4-ylphenyl)pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1C(C=C1F)=CC=C1N1CCOCC1 AIYDLANGWZEMCT-LBPRGKRZSA-N 0.000 description 1
• LJWJDYWBVKDPSE-QRPNPIFTSA-N (3s)-3-amino-1-(4-bromo-2-fluorophenyl)pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(Br)C=C1F LJWJDYWBVKDPSE-QRPNPIFTSA-N 0.000 description 1
• NKZGEZBMAKETQG-WCCKRBBISA-N (3s)-3-amino-1-(5-bromo-1,3-thiazol-2-yl)pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=NC=C(Br)S1 NKZGEZBMAKETQG-WCCKRBBISA-N 0.000 description 1
• HJFYWXFOVLIWJG-KLXURFKVSA-N (3s)-3-amino-1-(5-iodopyridin-2-yl)pyrrolidin-2-one;dihydrochloride Chemical compound Cl.Cl.O=C1[C@@H](N)CCN1C1=CC=C(I)C=N1 HJFYWXFOVLIWJG-KLXURFKVSA-N 0.000 description 1
• DVSUQHFIAMENSN-ZDUSSCGKSA-N (3s)-3-amino-1-(5-phenylpyridin-2-yl)pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1C1=CC=C(C=2C=CC=CC=2)C=N1 DVSUQHFIAMENSN-ZDUSSCGKSA-N 0.000 description 1
• XCFJACABDZCYEU-ZOWNYOTGSA-N (3s)-3-amino-1-[2-fluoro-4-(2-nitrophenyl)phenyl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CC=CC=2)[N+]([O-])=O)C=C1F XCFJACABDZCYEU-ZOWNYOTGSA-N 0.000 description 1
• NCEABBAJQQBIAJ-LBPRGKRZSA-N (3s)-3-amino-1-[2-fluoro-4-(pyrrolidine-1-carbonyl)phenyl]pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1C1=CC=C(C(=O)N2CCCC2)C=C1F NCEABBAJQQBIAJ-LBPRGKRZSA-N 0.000 description 1
• YLSGTGZGMQRMOL-ZOWNYOTGSA-N (3s)-3-amino-1-[4-(3-chloropyridin-4-yl)-2-fluorophenyl]pyrrolidin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CN=CC=2)Cl)C=C1F YLSGTGZGMQRMOL-ZOWNYOTGSA-N 0.000 description 1
• VWYOOPNDTSRENF-ZDUSSCGKSA-N (3s)-3-amino-1-[5-(2-methylsulfonylphenyl)pyridin-2-yl]pyrrolidin-2-one Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 VWYOOPNDTSRENF-ZDUSSCGKSA-N 0.000 description 1
• BFURPFLMCMPPPP-YDALLXLXSA-N (3s)-3-amino-1-[5-(2-nitrophenyl)pyridin-2-yl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CC=CC=2)[N+]([O-])=O)C=N1 BFURPFLMCMPPPP-YDALLXLXSA-N 0.000 description 1
• ZDYPVFRGHLYKEK-NTISSMGPSA-N (3s)-3-amino-1-[5-(2-tert-butylphenyl)pyridin-2-yl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.CC(C)(C)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 ZDYPVFRGHLYKEK-NTISSMGPSA-N 0.000 description 1
• AQQMYMSCULCYFL-ZOWNYOTGSA-N (3s)-3-amino-1-[5-[2-(trifluoromethyl)phenyl]pyridin-2-yl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CC=CC=2)C(F)(F)F)C=N1 AQQMYMSCULCYFL-ZOWNYOTGSA-N 0.000 description 1
• RETNMHLQDWDDAQ-UHFFFAOYSA-N (4-propylpyridin-3-yl)boronic acid Chemical compound CCCC1=CC=NC=C1B(O)O RETNMHLQDWDDAQ-UHFFFAOYSA-N 0.000 description 1
• JFCLNCVCDFUJPO-UHFFFAOYSA-N (5-chlorothiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)S1 JFCLNCVCDFUJPO-UHFFFAOYSA-N 0.000 description 1
• KITGLYBJJXWZLG-SNAWJCMRSA-N (e)-2-(5-chlorothiophen-2-yl)prop-1-ene-1-sulfonyl chloride Chemical compound ClS(=O)(=O)\C=C(/C)C1=CC=C(Cl)S1 KITGLYBJJXWZLG-SNAWJCMRSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
• HTZGPEHWQCRXGZ-UHFFFAOYSA-N 1-(5-chlorothiophen-2-yl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)S1 HTZGPEHWQCRXGZ-UHFFFAOYSA-N 0.000 description 1
• MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• ALAQDUSTXPEHMH-UHFFFAOYSA-N 1-bromo-2-methylsulfanylbenzene Chemical compound CSC1=CC=CC=C1Br ALAQDUSTXPEHMH-UHFFFAOYSA-N 0.000 description 1
• MMORVPBHAHXAHH-UHFFFAOYSA-N 1-bromo-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC=C1Br MMORVPBHAHXAHH-UHFFFAOYSA-N 0.000 description 1
• DSMRKVAAKZIVQL-UHFFFAOYSA-N 1-bromo-2-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1Br DSMRKVAAKZIVQL-UHFFFAOYSA-N 0.000 description 1
• KOQIUCGNMKMESZ-UHFFFAOYSA-N 1-bromocyclohexa-2,4-diene-1-sulfonamide Chemical compound NS(=O)(=O)C1(Br)CC=CC=C1 KOQIUCGNMKMESZ-UHFFFAOYSA-N 0.000 description 1
• 125000006083 1-bromoethyl group Chemical group 0.000 description 1
• JTPNRXUCIXHOKM-UHFFFAOYSA-N 1-chloronaphthalene Chemical compound C1=CC=C2C(Cl)=CC=CC2=C1 JTPNRXUCIXHOKM-UHFFFAOYSA-N 0.000 description 1
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
• PUEBUBYUYPLMLU-UHFFFAOYSA-N 1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazole Chemical compound CN1C=CN=C1B1OC(C)(C)C(C)(C)O1 PUEBUBYUYPLMLU-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
• UPUWMQZUXFAUCJ-UHFFFAOYSA-N 2,5-dihydro-1,2-thiazole Chemical compound C1SNC=C1 UPUWMQZUXFAUCJ-UHFFFAOYSA-N 0.000 description 1
• NSFACMRSMSAWMS-UHFFFAOYSA-N 2-(2-bromoethyl)-5-chlorothiophene Chemical compound ClC1=CC=C(CCBr)S1 NSFACMRSMSAWMS-UHFFFAOYSA-N 0.000 description 1
• XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
• FFPYIDHZXPSZRQ-UHFFFAOYSA-N 2-(5-chlorothiophen-2-yl)ethanol Chemical compound OCCC1=CC=C(Cl)S1 FFPYIDHZXPSZRQ-UHFFFAOYSA-N 0.000 description 1
• BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
• JOJUMQGSSUKPES-UQKRIMTDSA-N 2-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]-n-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1N1C(=O)[C@@H](N)CC1 JOJUMQGSSUKPES-UQKRIMTDSA-N 0.000 description 1
• YEZGKSBOSOHAIB-ZOWNYOTGSA-N 2-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]benzenesulfonamide;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CC=CC=2)S(N)(=O)=O)C=C1F YEZGKSBOSOHAIB-ZOWNYOTGSA-N 0.000 description 1
• ZAPDNYSPBIXARL-RSAXXLAASA-N 2-[6-[(3s)-3-amino-2-oxopyrrolidin-1-yl]pyridin-3-yl]-n,n-dimethylbenzamide;hydrochloride Chemical compound Cl.CN(C)C(=O)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 ZAPDNYSPBIXARL-RSAXXLAASA-N 0.000 description 1
• MZFRIGRMMIGCRY-ZOWNYOTGSA-N 2-[6-[(3s)-3-amino-2-oxopyrrolidin-1-yl]pyridin-3-yl]-n-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 MZFRIGRMMIGCRY-ZOWNYOTGSA-N 0.000 description 1
• UDPCHBRQYHMICK-UQKRIMTDSA-N 2-[6-[(3s)-3-amino-2-oxopyrrolidin-1-yl]pyridin-3-yl]benzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C=2C(=CC=CC=2)C#N)C=N1 UDPCHBRQYHMICK-UQKRIMTDSA-N 0.000 description 1
• RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
• BANOTGHIHYMTDL-UHFFFAOYSA-N 2-bromo-1-methylimidazole Chemical compound CN1C=CN=C1Br BANOTGHIHYMTDL-UHFFFAOYSA-N 0.000 description 1
• OGYMDBJRCOBHEY-UHFFFAOYSA-N 2-bromo-n,n-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC=C1Br OGYMDBJRCOBHEY-UHFFFAOYSA-N 0.000 description 1
• VFPWGZNNRSQPBT-UHFFFAOYSA-N 2-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1Br VFPWGZNNRSQPBT-UHFFFAOYSA-N 0.000 description 1
• AFMPMSCZPVNPEM-UHFFFAOYSA-N 2-bromobenzonitrile Chemical compound BrC1=CC=CC=C1C#N AFMPMSCZPVNPEM-UHFFFAOYSA-N 0.000 description 1
• VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• PHMRPWPDDRGGGF-UHFFFAOYSA-N 2-bromoprop-1-ene Chemical compound CC(Br)=C PHMRPWPDDRGGGF-UHFFFAOYSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 1
• CGYGETOMCSJHJU-UHFFFAOYSA-N 2-chloronaphthalene Chemical compound C1=CC=CC2=CC(Cl)=CC=C21 CGYGETOMCSJHJU-UHFFFAOYSA-N 0.000 description 1
• OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
• WCSZDMUTWBSGAW-UHFFFAOYSA-N 2-fluoro-4-(2-methylsulfonylphenyl)aniline Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=CC=C(N)C(F)=C1 WCSZDMUTWBSGAW-UHFFFAOYSA-N 0.000 description 1
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
• WJQOZHYUIDYNHM-UHFFFAOYSA-N 2-tert-Butylphenol Chemical compound CC(C)(C)C1=CC=CC=C1O WJQOZHYUIDYNHM-UHFFFAOYSA-N 0.000 description 1
• ACNUVXZPCIABEX-UHFFFAOYSA-N 3',6'-diaminospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(N)C=C1OC1=CC(N)=CC=C21 ACNUVXZPCIABEX-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• YNDAMDVOGKACTP-UHFFFAOYSA-N 3-aminopyrrolidin-2-one Chemical compound NC1CCNC1=O YNDAMDVOGKACTP-UHFFFAOYSA-N 0.000 description 1
• HDYNIWBNWMFBDO-UHFFFAOYSA-N 3-bromo-2-chloropyridine Chemical compound ClC1=NC=CC=C1Br HDYNIWBNWMFBDO-UHFFFAOYSA-N 0.000 description 1
• PPXNTHZLYOJZCA-UHFFFAOYSA-N 3-bromo-4-propylpyridine Chemical compound CCCC1=CC=NC=C1Br PPXNTHZLYOJZCA-UHFFFAOYSA-N 0.000 description 1
• HCOPIUVJCIZALB-UHFFFAOYSA-N 3-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=CN=C1C#N HCOPIUVJCIZALB-UHFFFAOYSA-N 0.000 description 1
• TZIZJTNBJVKCSZ-PPHPATTJSA-N 4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluoro-n,n-dimethylbenzamide;hydrochloride Chemical compound Cl.FC1=CC(C(=O)N(C)C)=CC=C1N1C(=O)[C@@H](N)CC1 TZIZJTNBJVKCSZ-PPHPATTJSA-N 0.000 description 1
• VKYSRSGABVBCBH-YDALLXLXSA-N 4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluoro-n-methyl-n-propan-2-ylbenzamide;hydrochloride Chemical compound Cl.FC1=CC(C(=O)N(C)C(C)C)=CC=C1N1C(=O)[C@@H](N)CC1 VKYSRSGABVBCBH-YDALLXLXSA-N 0.000 description 1
• AGRDQGYRAKCCQO-FVGYRXGTSA-N 4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluoro-n-methylbenzamide;hydrochloride Chemical compound Cl.FC1=CC(C(=O)NC)=CC=C1N1C(=O)[C@@H](N)CC1 AGRDQGYRAKCCQO-FVGYRXGTSA-N 0.000 description 1
• SFJOBKAYDRGEJR-QRPNPIFTSA-N 4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorobenzamide;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C(N)=O)C=C1F SFJOBKAYDRGEJR-QRPNPIFTSA-N 0.000 description 1
• FPQVDVSKGUESAZ-FVGYRXGTSA-N 4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorobenzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1C1=CC=C(C#N)C=C1F FPQVDVSKGUESAZ-FVGYRXGTSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• IOTSLMMLLXTNNH-UHFFFAOYSA-N 4-bromo-1-methylimidazole Chemical compound CN1C=NC(Br)=C1 IOTSLMMLLXTNNH-UHFFFAOYSA-N 0.000 description 1
• GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 1
• HATLLUIOEIXWGD-UHFFFAOYSA-N 5-bromo-1-methylimidazole Chemical compound CN1C=NC=C1Br HATLLUIOEIXWGD-UHFFFAOYSA-N 0.000 description 1
• JHJAVTDTHYISNR-UHFFFAOYSA-N 5-chlorothieno[3,2-b]thiophene Chemical compound S1C=CC2=C1C=C(Cl)S2 JHJAVTDTHYISNR-UHFFFAOYSA-N 0.000 description 1
• IVILGUFRMDBUEQ-UHFFFAOYSA-N 5-iodopyridin-2-amine Chemical compound NC1=CC=C(I)C=N1 IVILGUFRMDBUEQ-UHFFFAOYSA-N 0.000 description 1
• RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
• 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
• 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• CTVSTIXWQXMHOL-SFHVURJKSA-N C(C)(C)(C)OC(N[C@@H]1C(N(CC1)C1=NC=C(C=C1)C1=C(C=CC=C1)OC(C)C)=O)=O Chemical compound C(C)(C)(C)OC(N[C@@H]1C(N(CC1)C1=NC=C(C=C1)C1=C(C=CC=C1)OC(C)C)=O)=O CTVSTIXWQXMHOL-SFHVURJKSA-N 0.000 description 1
• MENLQOBHRGZSPO-KRWDZBQOSA-N C(C)(C)(C)OC(N[C@@H]1C(N(CC1)C1=NC=C(C=C1)C1=C(C=CC=C1)S(=O)(=O)N(C)C)=O)=O Chemical compound C(C)(C)(C)OC(N[C@@H]1C(N(CC1)C1=NC=C(C=C1)C1=C(C=CC=C1)S(=O)(=O)N(C)C)=O)=O MENLQOBHRGZSPO-KRWDZBQOSA-N 0.000 description 1
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 206010053567 Coagulopathies Diseases 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
• 102000005927 Cysteine Proteases Human genes 0.000 description 1
• 108010005843 Cysteine Proteases Proteins 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• CZCKWOKUNKDIDJ-UHFFFAOYSA-N N,N,5-trimethyl-1H-imidazol-2-amine Chemical compound CN(C)C=1NC=C(N=1)C CZCKWOKUNKDIDJ-UHFFFAOYSA-N 0.000 description 1
• BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• KFLARKLJVSLCNM-FVGYRXGTSA-N N-[4-[(3S)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]methanesulfonamide hydrochloride Chemical compound CS(=O)(=O)NC1=CC(=C(C=C1)N2CC[C@@H](C2=O)N)F.Cl KFLARKLJVSLCNM-FVGYRXGTSA-N 0.000 description 1
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
• 206010029240 Neuritis Diseases 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 206010061876 Obstruction Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 240000006711 Pistacia vera Species 0.000 description 1
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 108010023197 Streptokinase Proteins 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 229940122388 Thrombin inhibitor Drugs 0.000 description 1
• 102000003938 Thromboxane Receptors Human genes 0.000 description 1
• 108090000300 Thromboxane Receptors Proteins 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• MXZNUGFCDVAXLG-CHWSQXEVSA-N [(2S)-1-[(2R)-3-methyl-2-(pyridine-4-carbonylamino)butanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@@H](NC(=O)c1ccncc1)C(=O)N1CCC[C@@H]1B(O)O MXZNUGFCDVAXLG-CHWSQXEVSA-N 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 206010000891 acute myocardial infarction Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 125000005103 alkyl silyl group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000001164 bioregulatory effect Effects 0.000 description 1
• 239000010836 blood and blood product Substances 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000023555 blood coagulation Effects 0.000 description 1
• 208000015294 blood coagulation disease Diseases 0.000 description 1
• 239000003114 blood coagulation factor Substances 0.000 description 1
• 229940125691 blood product Drugs 0.000 description 1
• 239000000337 buffer salt Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 229910001424 calcium ion Inorganic materials 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000001715 carbamic acids Chemical class 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 210000003850 cellular structure Anatomy 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 239000003593 chromogenic compound Substances 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 239000012045 crude solution Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• WJYHCYBNUJVCEH-UHFFFAOYSA-N cyclohexane;ethoxyethane Chemical compound CCOCC.C1CCCCC1 WJYHCYBNUJVCEH-UHFFFAOYSA-N 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• RPHGETHJNRVQLW-UHFFFAOYSA-N ethyl 2-(5-chlorothiophen-2-yl)-2-hydroxypropane-1-sulfonate Chemical compound CCOS(=O)(=O)CC(C)(O)C1=CC=C(Cl)S1 RPHGETHJNRVQLW-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000003176 fibrotic effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000007478 fluorogenic assay Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• MYDZUHZYHKZGBW-UHFFFAOYSA-N formamide;sodium Chemical compound [Na].NC=O MYDZUHZYHKZGBW-UHFFFAOYSA-N 0.000 description 1
• 150000004674 formic acids Chemical class 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 230000009931 harmful effect Effects 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• 230000002439 hemostatic effect Effects 0.000 description 1
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• 239000003509 long acting drug Substances 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229940126601 medicinal product Drugs 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940071648 metered dose inhaler Drugs 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 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
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• ANEOQJILAXCBEN-UHFFFAOYSA-N n-(2-bromophenyl)-n-methylmethanesulfonamide Chemical compound CS(=O)(=O)N(C)C1=CC=CC=C1Br ANEOQJILAXCBEN-UHFFFAOYSA-N 0.000 description 1
• UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
• LLEKXHSXQCLGJL-UQKRIMTDSA-N n-[2-[6-[(3s)-3-amino-2-oxopyrrolidin-1-yl]pyridin-3-yl]phenyl]-n-methylmethanesulfonamide;hydrochloride Chemical compound Cl.CS(=O)(=O)N(C)C1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 LLEKXHSXQCLGJL-UQKRIMTDSA-N 0.000 description 1
• VELVNSDTIIJIAM-ZOWNYOTGSA-N n-[2-[6-[(3s)-3-amino-2-oxopyrrolidin-1-yl]pyridin-3-yl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.CS(=O)(=O)NC1=CC=CC=C1C1=CC=C(N2C([C@@H](N)CC2)=O)N=C1 VELVNSDTIIJIAM-ZOWNYOTGSA-N 0.000 description 1
• YGMMPHOVFSCJGW-NSHDSACASA-N n-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]-2-methylpropanamide Chemical compound FC1=CC(NC(=O)C(C)C)=CC=C1N1C(=O)[C@@H](N)CC1 YGMMPHOVFSCJGW-NSHDSACASA-N 0.000 description 1
• NOVKNESQIDLSJP-YDALLXLXSA-N n-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]-n-propan-2-ylformamide;hydrochloride Chemical compound Cl.FC1=CC(N(C=O)C(C)C)=CC=C1N1C(=O)[C@@H](N)CC1 NOVKNESQIDLSJP-YDALLXLXSA-N 0.000 description 1
• UAXNLAQGRPOAJH-JTQLQIEISA-N n-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]acetamide Chemical compound FC1=CC(NC(=O)C)=CC=C1N1C(=O)[C@@H](N)CC1 UAXNLAQGRPOAJH-JTQLQIEISA-N 0.000 description 1
• APWHKSLYYAJXQS-JTQLQIEISA-N n-[4-[(3s)-3-amino-2-oxopyrrolidin-1-yl]-3-fluorophenyl]propanamide Chemical compound FC1=CC(NC(=O)CC)=CC=C1N1C(=O)[C@@H](N)CC1 APWHKSLYYAJXQS-JTQLQIEISA-N 0.000 description 1
• 238000004172 nitrogen cycle Methods 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229940019331 other antithrombotic agent in atc Drugs 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229960003540 oxyquinoline Drugs 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 235000002651 pink gum Nutrition 0.000 description 1
• 244000087877 pink gum Species 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000006410 propenylene group Chemical group 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 230000001110 prostacyclinlike Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• SCFVLCBATVDKDN-UHFFFAOYSA-N pyrrolidin-2-one;2,2,2-trifluoroacetic acid Chemical compound O=C1CCCN1.OC(=O)C(F)(F)F SCFVLCBATVDKDN-UHFFFAOYSA-N 0.000 description 1
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
• 238000011470 radical surgery Methods 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 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 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 239000011775 sodium fluoride Substances 0.000 description 1
• 235000013024 sodium fluoride Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000002594 sorbent Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000012086 standard solution Substances 0.000 description 1
• 229940032147 starch Drugs 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229960005202 streptokinase Drugs 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• ZJFSKTHRACPMJQ-AWEZNQCLSA-N tert-butyl N-[(3S)-1-[2-fluoro-4-(propan-2-ylamino)phenyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H]1C(N(CC1)C1=C(C=C(C=C1)NC(C)C)F)=O)=O ZJFSKTHRACPMJQ-AWEZNQCLSA-N 0.000 description 1
• QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
• NPINOJIHUWIZGH-HNNXBMFYSA-N tert-butyl n-[(2s)-1-(3-fluoro-4-morpholin-4-ylanilino)-4-hydroxy-1-oxobutan-2-yl]carbamate Chemical compound FC1=CC(NC(=O)[C@H](CCO)NC(=O)OC(C)(C)C)=CC=C1N1CCOCC1 NPINOJIHUWIZGH-HNNXBMFYSA-N 0.000 description 1
• FXRBSVMUCGXHAI-NSHDSACASA-N tert-butyl n-[(3s)-1-(4-bromo-2-fluorophenyl)-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(Br)C=C1F FXRBSVMUCGXHAI-NSHDSACASA-N 0.000 description 1
• PBIALWHBAAHUFR-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[2-fluoro-4-(2-methylpropanoylamino)phenyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound FC1=CC(NC(=O)C(C)C)=CC=C1N1C(=O)[C@@H](NC(=O)OC(C)(C)C)CC1 PBIALWHBAAHUFR-AWEZNQCLSA-N 0.000 description 1
• QCHNVJKEJLZDSI-KRWDZBQOSA-N tert-butyl n-[(3s)-1-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(C=2C(=CC=CC=2)S(C)(=O)=O)C=C1F QCHNVJKEJLZDSI-KRWDZBQOSA-N 0.000 description 1
• IPISLNJJYLDSQE-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[4-(dimethylamino)phenyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound C1=CC(N(C)C)=CC=C1N1C(=O)[C@@H](NC(=O)OC(C)(C)C)CC1 IPISLNJJYLDSQE-AWEZNQCLSA-N 0.000 description 1
• GVCUZCJNHRCOJL-KRWDZBQOSA-N tert-butyl n-[(3s)-1-[5-(2-cyanophenyl)pyridin-2-yl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(C=2C(=CC=CC=2)C#N)C=N1 GVCUZCJNHRCOJL-KRWDZBQOSA-N 0.000 description 1
• BMPXBBKQRYLHSH-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[5-(2-nitrophenyl)pyridin-2-yl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(C=2C(=CC=CC=2)[N+]([O-])=O)C=N1 BMPXBBKQRYLHSH-HNNXBMFYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• AGJMQNHFJCOMQE-UHFFFAOYSA-N thieno[2,3-b]pyridine-2-sulfonamide Chemical compound C1=CN=C2SC(S(=O)(=O)N)=CC2=C1 AGJMQNHFJCOMQE-UHFFFAOYSA-N 0.000 description 1
• 239000003868 thrombin inhibitor Substances 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 108010036927 trypsin-like serine protease Proteins 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1