NO318963B1 - Forbindelser og fremgangsmate for fremstilling derav, terapeutiske preparater, anvendelser av forbindelsene og mellomprodukter. - Google Patents

Info

Publication number

NO318963B1

NO318963B1 NO20010252A NO20010252A NO318963B1 NO 318963 B1 NO318963 B1 NO 318963B1 NO 20010252 A NO20010252 A NO 20010252A NO 20010252 A NO20010252 A NO 20010252A NO 318963 B1 NO318963 B1 NO 318963B1

Authority

NO

Norway

Prior art keywords

amino

piperidyl

groups

ethyl

butanoyl

Prior art date

1998-07-17

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 105
• 238000002360 preparation method Methods 0.000 title claims description 20
• 238000000034 method Methods 0.000 title claims description 11
• 230000001225 therapeutic effect Effects 0.000 title claims description 5
• 239000000543 intermediate Substances 0.000 title description 2
• 102000008946 Fibrinogen Human genes 0.000 claims abstract description 9
• 108010049003 Fibrinogen Proteins 0.000 claims abstract description 9
• 229940012952 fibrinogen Drugs 0.000 claims abstract description 9
• 239000003146 anticoagulant agent Substances 0.000 claims abstract description 7
• -1 benzodioxanyl Chemical group 0.000 claims description 100
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 81
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 239000002253 acid Substances 0.000 claims description 30
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 27
• 229910052736 halogen Inorganic materials 0.000 claims description 21
• 150000002367 halogens Chemical group 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 125000001624 naphthyl group Chemical group 0.000 claims description 14
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 13
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 125000001544 thienyl group Chemical group 0.000 claims description 10
• 238000011282 treatment Methods 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• 125000002950 monocyclic group Chemical group 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 125000004414 alkyl thio group Chemical group 0.000 claims description 8
• 125000002541 furyl group Chemical group 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000005493 quinolyl group Chemical group 0.000 claims description 8
• 208000007536 Thrombosis Diseases 0.000 claims description 7
• 150000007513 acids Chemical class 0.000 claims description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 125000006242 amine protecting group Chemical group 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000003367 polycyclic group Chemical group 0.000 claims description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
• 230000001732 thrombotic effect Effects 0.000 claims description 5
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 4
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
• ZYUZLEUJKZZXNN-UHFFFAOYSA-N C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 Chemical group C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 ZYUZLEUJKZZXNN-UHFFFAOYSA-N 0.000 claims description 4
• 230000002776 aggregation Effects 0.000 claims description 4
• 238000004220 aggregation Methods 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
• 235000019260 propionic acid Nutrition 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims description 2
• 229940127217 antithrombotic drug Drugs 0.000 claims description 2
• 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 claims description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
• 125000006267 biphenyl group Chemical group 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• LKTHYTRIPCUTPA-MUUNZHRXSA-N (2r)-2-(naphthalen-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C([C@H](C(=O)O)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LKTHYTRIPCUTPA-MUUNZHRXSA-N 0.000 claims 1
• LKTHYTRIPCUTPA-NDEPHWFRSA-N (2s)-2-(naphthalen-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LKTHYTRIPCUTPA-NDEPHWFRSA-N 0.000 claims 1
• UHCCPWHFFNIPMA-LJAQVGFWSA-N (2s)-2-[(6-methoxynaphthalen-2-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C([C@H](NS(=O)(=O)C1=CC2=CC=C(C=C2C=C1)OC)C(O)=O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 UHCCPWHFFNIPMA-LJAQVGFWSA-N 0.000 claims 1
• IOBQMMZLUKYEFA-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C2OCOC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 IOBQMMZLUKYEFA-UHFFFAOYSA-N 0.000 claims 1
• UIZJVJIPNICPRR-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C2OCCOC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 UIZJVJIPNICPRR-UHFFFAOYSA-N 0.000 claims 1
• LBNPPEZYFNFKOU-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-5-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C2CCCC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LBNPPEZYFNFKOU-UHFFFAOYSA-N 0.000 claims 1
• XIKCEQQHAVWNLJ-UHFFFAOYSA-N 2-(benzenesulfonamido)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=CC=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 XIKCEQQHAVWNLJ-UHFFFAOYSA-N 0.000 claims 1
• VWRIYFAXQVUQOW-UHFFFAOYSA-N 2-(naphthalen-1-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 VWRIYFAXQVUQOW-UHFFFAOYSA-N 0.000 claims 1
• KCDOPSBGYCXZKY-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[3-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]propanoylamino]propanoic acid Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CCNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 KCDOPSBGYCXZKY-UHFFFAOYSA-N 0.000 claims 1
• GNMHUXMSIYFUSP-UHFFFAOYSA-N 2-[(2,5-dimethylfuran-3-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound O1C(C)=CC(S(=O)(=O)NC(CNC(=O)CNC(=O)C(CCC2CCNCC2)CCC2CCNCC2)C(O)=O)=C1C GNMHUXMSIYFUSP-UHFFFAOYSA-N 0.000 claims 1
• JBTXHSCCDPPZGV-UHFFFAOYSA-N 2-[(3-nitrophenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=CC([N+]([O-])=O)=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 JBTXHSCCDPPZGV-UHFFFAOYSA-N 0.000 claims 1
• HWMYBEQUAQSLEZ-UHFFFAOYSA-N 2-[(4-chloronaphthalen-1-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C(Cl)C2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 HWMYBEQUAQSLEZ-UHFFFAOYSA-N 0.000 claims 1
• JPQMDEIZRIKMIV-UHFFFAOYSA-N 2-[(4-fluoronaphthalen-1-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C(F)C2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 JPQMDEIZRIKMIV-UHFFFAOYSA-N 0.000 claims 1
• GQWSPVQLDWGSDD-UHFFFAOYSA-N 2-[(4-methylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 GQWSPVQLDWGSDD-UHFFFAOYSA-N 0.000 claims 1
• FVSGEKCNSJWKAE-UHFFFAOYSA-N 2-[(4-phenylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 FVSGEKCNSJWKAE-UHFFFAOYSA-N 0.000 claims 1
• HIAODQZBASRNQC-UHFFFAOYSA-N 2-[(5-phenylthiophen-2-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C(C=2C=CC=CC=2)SC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 HIAODQZBASRNQC-UHFFFAOYSA-N 0.000 claims 1
• BLSUBPWDEGUKBR-UHFFFAOYSA-N 2-[(6,7-dimethoxynaphthalen-2-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C1=C2C=C(OC)C(OC)=CC2=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 BLSUBPWDEGUKBR-UHFFFAOYSA-N 0.000 claims 1
• RGJXSHPBRWANLX-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C=C2OCOC2=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 RGJXSHPBRWANLX-UHFFFAOYSA-N 0.000 claims 1
• KUHCZKMJIRSXLW-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(pyridin-3-ylsulfonylamino)propanoic acid Chemical compound C=1C=CN=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 KUHCZKMJIRSXLW-UHFFFAOYSA-N 0.000 claims 1
• PXRDKOHVRWHLPD-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(thiophen-2-ylsulfonylamino)propanoic acid Chemical compound C=1C=CSC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 PXRDKOHVRWHLPD-UHFFFAOYSA-N 0.000 claims 1
• AGQVJZJWIYOZNW-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 AGQVJZJWIYOZNW-UHFFFAOYSA-N 0.000 claims 1
• NPQFILBXIYFGLG-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[[3-(trifluoromethyl)phenyl]sulfonylamino]propanoic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 NPQFILBXIYFGLG-UHFFFAOYSA-N 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 3
• 229960004676 antithrombotic agent Drugs 0.000 abstract description 2
• 239000007858 starting material Substances 0.000 description 162
• 238000005160 1H NMR spectroscopy Methods 0.000 description 136
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 136
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 90
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 43
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
• 238000005481 NMR spectroscopy Methods 0.000 description 30
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 28
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• 239000000243 solution Substances 0.000 description 22
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
• 238000003756 stirring Methods 0.000 description 17
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 14
• 239000007787 solid Substances 0.000 description 14
• 239000000203 mixture Substances 0.000 description 13
• 101150041968 CDC13 gene Proteins 0.000 description 12
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• WIXGNJBRAATAKF-UHFFFAOYSA-N 2-[[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoyl]amino]acetic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NCC(O)=O)CCC1CCN(C(=O)OC(C)(C)C)CC1 WIXGNJBRAATAKF-UHFFFAOYSA-N 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 210000004369 blood Anatomy 0.000 description 9
• 239000008280 blood Substances 0.000 description 9
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
• 210000004623 platelet-rich plasma Anatomy 0.000 description 8
• 229940126214 compound 3 Drugs 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 241000700198 Cavia Species 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• DWAJUHMLNRLVJK-AREMUKBSSA-N (3r)-1-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoyl]piperidine-3-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)N1C[C@@H](CCC1)C(O)=O)CCC1CCN(C(=O)OC(C)(C)C)CC1 DWAJUHMLNRLVJK-AREMUKBSSA-N 0.000 description 4
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 229940125782 compound 2 Drugs 0.000 description 4
• 230000008018 melting Effects 0.000 description 4
• 238000002844 melting Methods 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
• KVCAWHUBSDCCNL-UUWRZZSWSA-N (2r)-3-[[2-[[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoyl]amino]acetyl]amino]-2-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NCC(=O)NC[C@@H](NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)C(O)=O)CCC1CCN(C(=O)OC(C)(C)C)CC1 KVCAWHUBSDCCNL-UUWRZZSWSA-N 0.000 description 3
• TVCVZPPTRJJNOP-UHFFFAOYSA-N 1,2-dihydropyridine-2-carboxylic acid Chemical compound OC(=O)C1NC=CC=C1 TVCVZPPTRJJNOP-UHFFFAOYSA-N 0.000 description 3
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
• GEBQVZKUMWMMSI-UHFFFAOYSA-N 3-[[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoyl]amino]-3-phenylpropanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NC(CC(O)=O)C=1C=CC=CC=1)CCC1CCN(C(=O)OC(C)(C)C)CC1 GEBQVZKUMWMMSI-UHFFFAOYSA-N 0.000 description 3
• WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 3
• 206010002388 Angina unstable Diseases 0.000 description 3
• 206010003178 Arterial thrombosis Diseases 0.000 description 3
• YIWHCWDLHQBZQH-UQKRIMTDSA-N Cl.C1=CC=CC2=CC(S(=O)(=O)N[C@@H](CN)C(=O)OCC)=CC=C21 Chemical compound Cl.C1=CC=CC2=CC(S(=O)(=O)N[C@@H](CN)C(=O)OCC)=CC=C21 YIWHCWDLHQBZQH-UQKRIMTDSA-N 0.000 description 3
• 229940126639 Compound 33 Drugs 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
• PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 208000007814 Unstable Angina Diseases 0.000 description 3
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 238000006243 chemical reaction Methods 0.000 description 3
• 229940126543 compound 14 Drugs 0.000 description 3
• 229940127204 compound 29 Drugs 0.000 description 3
• 229940126540 compound 41 Drugs 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 238000011835 investigation Methods 0.000 description 3
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 3
• 210000002381 plasma Anatomy 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 2
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 2
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 2
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 2
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
• 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 2
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 2
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 2
• VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 description 2
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 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 2
• QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 2
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 2
• QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 2
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
• FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 2
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 2
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
• JDOAIEXUQGTIFK-UHFFFAOYSA-N 2-aminopropanoic acid;dihydrochloride Chemical compound Cl.Cl.CC(N)C(O)=O JDOAIEXUQGTIFK-UHFFFAOYSA-N 0.000 description 2
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 2
• DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 2
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
• BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 2
• DTGHUWCTBRHBAR-UHFFFAOYSA-N 4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(O)=O)CCC1CCN(C(=O)OC(C)(C)C)CC1 DTGHUWCTBRHBAR-UHFFFAOYSA-N 0.000 description 2
• DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 2
• VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 2
• XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 2
• 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 2
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 2
• HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 2
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 2
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
• 208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 2
• OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 2
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 2
• PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 2
• 229940126657 Compound 17 Drugs 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 2
• AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 2
• 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 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 2
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000004931 aggregating effect Effects 0.000 description 2
• 238000002399 angioplasty Methods 0.000 description 2
• 230000000702 anti-platelet effect Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
• 229940125773 compound 10 Drugs 0.000 description 2
• 229940125797 compound 12 Drugs 0.000 description 2
• 229940125758 compound 15 Drugs 0.000 description 2
• 229940126142 compound 16 Drugs 0.000 description 2
• 229940126086 compound 21 Drugs 0.000 description 2
• 229940126208 compound 22 Drugs 0.000 description 2
• 229940125833 compound 23 Drugs 0.000 description 2
• 229940125961 compound 24 Drugs 0.000 description 2
• 229940125846 compound 25 Drugs 0.000 description 2
• 229940125851 compound 27 Drugs 0.000 description 2
• 229940125877 compound 31 Drugs 0.000 description 2
• 229940125807 compound 37 Drugs 0.000 description 2
• 229940125936 compound 42 Drugs 0.000 description 2
• 229940127271 compound 49 Drugs 0.000 description 2
• 229940125898 compound 5 Drugs 0.000 description 2
• 229940126545 compound 53 Drugs 0.000 description 2
• 229940127113 compound 57 Drugs 0.000 description 2
• 229940125900 compound 59 Drugs 0.000 description 2
• 229940126179 compound 72 Drugs 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 2
• WFFNRMTWMDBKDZ-MERQFXBCSA-N ethyl (2s)-3-amino-2-(phenylmethoxycarbonylamino)propanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@H](CN)NC(=O)OCC1=CC=CC=C1 WFFNRMTWMDBKDZ-MERQFXBCSA-N 0.000 description 2
• GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 2
• RJCGNNHKSNIUAT-UHFFFAOYSA-N ethyl 3-aminopropanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CCN RJCGNNHKSNIUAT-UHFFFAOYSA-N 0.000 description 2
• MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 2
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
• 238000004108 freeze drying Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
• 229940040692 lithium hydroxide monohydrate Drugs 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
• 238000005259 measurement Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 2
• OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 2
• IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
• REQJQNZFBVALED-QDSLRZTOSA-N (2r)-2-(naphthalen-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C([C@H](C(=O)O)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 REQJQNZFBVALED-QDSLRZTOSA-N 0.000 description 1
• SBTKTTGTVUCKTI-GFCCVEGCSA-N (2r)-3-amino-2-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)N[C@H](CN)C(O)=O)=CC=C21 SBTKTTGTVUCKTI-GFCCVEGCSA-N 0.000 description 1
• HHPGQKZOPPDLNH-NWAAXCJESA-N (2r,3r)-2,3-dihydroxybutanedioic acid;ethyl (3r)-piperidine-3-carboxylate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CCOC(=O)[C@@H]1CCCNC1 HHPGQKZOPPDLNH-NWAAXCJESA-N 0.000 description 1
• YJJALQADJVKUHS-IKXQUJFKSA-N (2s)-2-(butylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NC[C@H](NS(=O)(=O)CCCC)C(O)=O)CCC1CCNCC1 YJJALQADJVKUHS-IKXQUJFKSA-N 0.000 description 1
• OBCPKLQXWSUYOQ-ROPHLPQBSA-N (2s)-2-(phenylmethoxycarbonylamino)-3-[3-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]propanoylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)CCNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 OBCPKLQXWSUYOQ-ROPHLPQBSA-N 0.000 description 1
• ULSKZPQDYXGNMQ-UJXPALLWSA-N (2s)-2-[(6-methoxynaphthalen-2-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C([C@H](NS(=O)(=O)C1=CC2=CC=C(C=C2C=C1)OC)C(O)=O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ULSKZPQDYXGNMQ-UJXPALLWSA-N 0.000 description 1
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
• GJXGFAWHJCIPDY-ASMAMLKCSA-N (3s)-4-(1,3-benzodioxol-5-ylmethylamino)-4-oxo-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]butanoic acid;dihydrochloride Chemical compound Cl.Cl.N([C@@H](CC(=O)O)C(=O)NCC=1C=C2OCOC2=CC=1)C(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 GJXGFAWHJCIPDY-ASMAMLKCSA-N 0.000 description 1
• YMONRPQXYHTCDZ-WLOLSGMKSA-N (3s)-4-(3-methoxyanilino)-4-oxo-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]butanoic acid;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC(NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)C(CCC2CCNCC2)CCC2CCNCC2)=C1 YMONRPQXYHTCDZ-WLOLSGMKSA-N 0.000 description 1
• HGPHNYOTIKGRCQ-LPCSYZHESA-N (3s)-4-[2-(4-methoxyphenyl)ethylamino]-4-oxo-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]butanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1CCNC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 HGPHNYOTIKGRCQ-LPCSYZHESA-N 0.000 description 1
• YCPMRUXYCNGERR-LPCSYZHESA-N (3s)-4-oxo-4-(3-phenylpropylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]butanoic acid;dihydrochloride Chemical compound Cl.Cl.N([C@@H](CC(=O)O)C(=O)NCCCC=1C=CC=CC=1)C(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 YCPMRUXYCNGERR-LPCSYZHESA-N 0.000 description 1
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
• STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• KWADQHDWHDJCLP-SNAWJCMRSA-N (e)-pent-1-ene-1-sulfonyl chloride Chemical compound CCC\C=C\S(Cl)(=O)=O KWADQHDWHDJCLP-SNAWJCMRSA-N 0.000 description 1
• ZRSGZIMDIHBXIN-UHFFFAOYSA-N 1,3-benzodioxole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2OCOC2=C1 ZRSGZIMDIHBXIN-UHFFFAOYSA-N 0.000 description 1
• ICUBASIDCXDQAW-UHFFFAOYSA-N 1,3-benzodioxole-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2OCOC2=C1 ICUBASIDCXDQAW-UHFFFAOYSA-N 0.000 description 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• RWCKBBSBRTUUHR-UHFFFAOYSA-N 1-benzofuran-2-sulfonyl chloride Chemical compound C1=CC=C2OC(S(=O)(=O)Cl)=CC2=C1 RWCKBBSBRTUUHR-UHFFFAOYSA-N 0.000 description 1
• FKIIVBOPAHICHQ-UHFFFAOYSA-N 1-benzothiophene-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=CC2=C1 FKIIVBOPAHICHQ-UHFFFAOYSA-N 0.000 description 1
• ILYVXUGGBVATGA-UHFFFAOYSA-N 1-carboxyethylazanium;chloride Chemical compound Cl.CC(N)C(O)=O ILYVXUGGBVATGA-UHFFFAOYSA-N 0.000 description 1
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
• RVWYPBARHGPULM-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2OCCC2=C1 RVWYPBARHGPULM-UHFFFAOYSA-N 0.000 description 1
• SWLIXMXSCZYVTQ-UHFFFAOYSA-N 2,3-dihydro-1h-indene-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2CCCC2=C1 SWLIXMXSCZYVTQ-UHFFFAOYSA-N 0.000 description 1
• PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
• GFFJSTHQILQFNQ-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-sulfonyl chloride Chemical compound CC1=NC(C)=C(S(Cl)(=O)=O)S1 GFFJSTHQILQFNQ-UHFFFAOYSA-N 0.000 description 1
• PIXAQZAVANAGLE-UHFFFAOYSA-N 2,5-dimethylfuran-3-sulfonyl chloride Chemical compound CC1=CC(S(Cl)(=O)=O)=C(C)O1 PIXAQZAVANAGLE-UHFFFAOYSA-N 0.000 description 1
• WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
• KHOHBKGNMAFPHZ-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2OCOC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 KHOHBKGNMAFPHZ-UHFFFAOYSA-N 0.000 description 1
• DVWSQUGCRVEZQK-UHFFFAOYSA-N 2-(1,3-benzodioxole-5-carbonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2OCOC2=CC=1C(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 DVWSQUGCRVEZQK-UHFFFAOYSA-N 0.000 description 1
• HQLFSIKIKIUXJH-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.N=1C2=CC=CC=C2SC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 HQLFSIKIKIUXJH-UHFFFAOYSA-N 0.000 description 1
• XKBSCAIMRZUXOX-UHFFFAOYSA-N 2-(1-benzofuran-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid Chemical compound C=1C2=CC=CC=C2OC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 XKBSCAIMRZUXOX-UHFFFAOYSA-N 0.000 description 1
• SDRWRMSMUKMOMK-UHFFFAOYSA-N 2-(1-benzothiophen-2-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C2=CC=CC=C2SC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 SDRWRMSMUKMOMK-UHFFFAOYSA-N 0.000 description 1
• FOJNXSGDAJYUMP-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2OCCC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 FOJNXSGDAJYUMP-UHFFFAOYSA-N 0.000 description 1
• LUERPZSVQQKWDB-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-5-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2CCCC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LUERPZSVQQKWDB-UHFFFAOYSA-N 0.000 description 1
• CVWFDEHLOZQNMY-UHFFFAOYSA-N 2-(3-chloropropylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NCC(C(=O)O)NS(=O)(=O)CCCCl)CCC1CCNCC1 CVWFDEHLOZQNMY-UHFFFAOYSA-N 0.000 description 1
• YSVNKRIHLJEBEW-UHFFFAOYSA-N 2-(benzylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=CC=1CS(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 YSVNKRIHLJEBEW-UHFFFAOYSA-N 0.000 description 1
• URFQRTFRTVZUJH-UHFFFAOYSA-N 2-(cyclohexylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CCCCC1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 URFQRTFRTVZUJH-UHFFFAOYSA-N 0.000 description 1
• VOIGSSVFSYRBPO-UHFFFAOYSA-N 2-(naphthalen-1-ylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=CC2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 VOIGSSVFSYRBPO-UHFFFAOYSA-N 0.000 description 1
• AVVNJNCOYNRQGU-UHFFFAOYSA-N 2-(naphthalen-2-ylmethylsulfonylamino)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=CC=1CS(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 AVVNJNCOYNRQGU-UHFFFAOYSA-N 0.000 description 1
• ZRZVROHWDBDIIA-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]propanoylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(O)=O)CNC(=O)C(C)NC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ZRZVROHWDBDIIA-UHFFFAOYSA-N 0.000 description 1
• IGSLOACMKBFJPI-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[3-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]propanoylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CCNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 IGSLOACMKBFJPI-UHFFFAOYSA-N 0.000 description 1
• PAPLOUTVJFNHQL-SXHZMTLWSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[[(3r)-1-[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]piperidine-3-carbonyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C([C@H](C1)C(=O)NCC(C(=O)O)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CCC1CCNCC1)CCC1CCNCC1 PAPLOUTVJFNHQL-SXHZMTLWSA-N 0.000 description 1
• VUFCWLDLITWVLN-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[[2-phenyl-2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)C(C=1C=CC=CC=1)NC(=O)C(CCC1CCNCC1)CCC1CCNCC1 VUFCWLDLITWVLN-UHFFFAOYSA-N 0.000 description 1
• LNPGQQQHBCEUGM-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-3-[[3-phenyl-3-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]butanoyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(O)=O)CNC(=O)CC(C)(C=1C=CC=CC=1)NC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LNPGQQQHBCEUGM-UHFFFAOYSA-N 0.000 description 1
• NFWZRPKMUVFPHT-UHFFFAOYSA-N 2-[(2,4-dimethyl-1,3-thiazol-5-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.S1C(C)=NC(C)=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 NFWZRPKMUVFPHT-UHFFFAOYSA-N 0.000 description 1
• TXMFDTRCZCAVDG-UHFFFAOYSA-N 2-[(2,5-dimethylfuran-3-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.O1C(C)=CC(S(=O)(=O)NC(CNC(=O)CNC(=O)C(CCC2CCNCC2)CCC2CCNCC2)C(O)=O)=C1C TXMFDTRCZCAVDG-UHFFFAOYSA-N 0.000 description 1
• REYYFWDPLQZQGE-UHFFFAOYSA-N 2-[(3,5-dimethyl-1,2-oxazol-4-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.CC1=NOC(C)=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 REYYFWDPLQZQGE-UHFFFAOYSA-N 0.000 description 1
• HEEDTSJUDYVJQO-UHFFFAOYSA-N 2-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid dihydrochloride Chemical compound Cl.Cl.CC1=NNC(=C1S(=O)(=O)NC(C(=O)O)CNC(CNC(C(CCC1CCNCC1)CCC1CCNCC1)=O)=O)C HEEDTSJUDYVJQO-UHFFFAOYSA-N 0.000 description 1
• GCKXSHKFNFVOBJ-UHFFFAOYSA-N 2-[(3-methylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.CC1=CC=CC(S(=O)(=O)NC(CNC(=O)CNC(=O)C(CCC2CCNCC2)CCC2CCNCC2)C(O)=O)=C1 GCKXSHKFNFVOBJ-UHFFFAOYSA-N 0.000 description 1
• SNRCCFNFHVGJAB-UHFFFAOYSA-N 2-[(4-chloronaphthalen-1-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 SNRCCFNFHVGJAB-UHFFFAOYSA-N 0.000 description 1
• USSJXSFOXLEQOE-UHFFFAOYSA-N 2-[(4-chlorophenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 USSJXSFOXLEQOE-UHFFFAOYSA-N 0.000 description 1
• CGRPLRUILWWYDH-UHFFFAOYSA-N 2-[(4-cyclohexylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(C2CCCCC2)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 CGRPLRUILWWYDH-UHFFFAOYSA-N 0.000 description 1
• VVPKPDCSFPZZDP-UHFFFAOYSA-N 2-[(4-fluoronaphthalen-1-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(F)C2=CC=CC=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 VVPKPDCSFPZZDP-UHFFFAOYSA-N 0.000 description 1
• XYNBNYZIHDZQBF-UHFFFAOYSA-N 2-[(4-fluorophenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(F)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 XYNBNYZIHDZQBF-UHFFFAOYSA-N 0.000 description 1
• OMBPEASFYHWXIJ-UHFFFAOYSA-N 2-[(4-methoxynaphthalen-1-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C12=CC=CC=C2C(OC)=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 OMBPEASFYHWXIJ-UHFFFAOYSA-N 0.000 description 1
• LIFHAWHWBDSNJB-UHFFFAOYSA-N 2-[(4-methoxyphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 LIFHAWHWBDSNJB-UHFFFAOYSA-N 0.000 description 1
• ZWSUEYQEPBBMPS-UHFFFAOYSA-N 2-[(4-methylsulfonylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC(S(=O)(=O)C)=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ZWSUEYQEPBBMPS-UHFFFAOYSA-N 0.000 description 1
• JFYYMPNUJJQEJP-UHFFFAOYSA-N 2-[(4-phenylphenyl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(C=2C=CC=CC=2)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 JFYYMPNUJJQEJP-UHFFFAOYSA-N 0.000 description 1
• RQOOVGOCNKBWKK-UHFFFAOYSA-N 2-[(6,7-dimethoxynaphthalen-2-yl)sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=C2C=C(OC)C(OC)=CC2=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 RQOOVGOCNKBWKK-UHFFFAOYSA-N 0.000 description 1
• ZISVUBIVRMHYOA-UHFFFAOYSA-N 2-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.CC1(C)C(CC2=O)CCC12CS(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ZISVUBIVRMHYOA-UHFFFAOYSA-N 0.000 description 1
• UIZBUNIQCAXHNN-KFZHMZRQSA-N 2-[[(e)-pent-1-enyl]sulfonylamino]-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NCC(NS(=O)(=O)/C=C/CCC)C(O)=O)CCC1CCNCC1 UIZBUNIQCAXHNN-KFZHMZRQSA-N 0.000 description 1
• NXGKPRKPUCSEIL-UHFFFAOYSA-N 2-acetamido-4-methyl-1,3-thiazole-5-sulfonyl chloride Chemical compound CC(=O)NC1=NC(C)=C(S(Cl)(=O)=O)S1 NXGKPRKPUCSEIL-UHFFFAOYSA-N 0.000 description 1
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
• ZXIORFCPRZTIBT-UHFFFAOYSA-N 2-aminobutanoic acid dihydrochloride Chemical compound Cl.Cl.C(C)C(C(=O)O)N ZXIORFCPRZTIBT-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• WNFRMBXFAYUDOL-UHFFFAOYSA-N 2-thiophen-2-ylbenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1C1=CC=CS1 WNFRMBXFAYUDOL-UHFFFAOYSA-N 0.000 description 1
• GZLPFEYTAAXJCP-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-sulfonyl chloride Chemical compound CC1=NOC(C)=C1S(Cl)(=O)=O GZLPFEYTAAXJCP-UHFFFAOYSA-N 0.000 description 1
• NBGSZCQLPLYKJH-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole-4-sulfonyl chloride Chemical compound CC1=NNC(C)=C1S(Cl)(=O)=O NBGSZCQLPLYKJH-UHFFFAOYSA-N 0.000 description 1
• KKYBJLWAFAXXFH-UHFFFAOYSA-N 3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2OCCOC2=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 KKYBJLWAFAXXFH-UHFFFAOYSA-N 0.000 description 1
• USRXLZXFQDLJFZ-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=C(OC)C(OC)=CC=C1C(CC(O)=O)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 USRXLZXFQDLJFZ-UHFFFAOYSA-N 0.000 description 1
• TXUNEAOHWPHJBQ-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(5,6,7,8-tetrahydronaphthalen-2-ylsulfonylamino)propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2CCCCC2=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 TXUNEAOHWPHJBQ-UHFFFAOYSA-N 0.000 description 1
• CBQVFSBJORKXIC-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(propan-2-ylsulfonylamino)propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NCC(NS(=O)(=O)C(C)C)C(O)=O)CCC1CCNCC1 CBQVFSBJORKXIC-UHFFFAOYSA-N 0.000 description 1
• KOPHMEMDIWBGRX-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(pyridin-3-ylsulfonylamino)propanoic acid;trihydrochloride Chemical compound Cl.Cl.Cl.C=1C=CN=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 KOPHMEMDIWBGRX-UHFFFAOYSA-N 0.000 description 1
• OSZARDVHQRQAAB-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(quinolin-8-ylsulfonylamino)propanoic acid;trihydrochloride Chemical compound Cl.Cl.Cl.C=1C=CC2=CC=CN=C2C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 OSZARDVHQRQAAB-UHFFFAOYSA-N 0.000 description 1
• PRIMCPUUCVVOPJ-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-(thiophen-2-ylsulfonylamino)propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=CSC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 PRIMCPUUCVVOPJ-UHFFFAOYSA-N 0.000 description 1
• ZGEOUSGFEIOZDC-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.CC1=CC(C)=CC(C)=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ZGEOUSGFEIOZDC-UHFFFAOYSA-N 0.000 description 1
• YYLVMWMZBHUTCB-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[(2-thiophen-2-ylphenyl)sulfonylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=C(C=2SC=CC=2)C=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 YYLVMWMZBHUTCB-UHFFFAOYSA-N 0.000 description 1
• QYELMFUTGFDVPD-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[(4-propylphenyl)sulfonylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC(CCC)=CC=C1S(=O)(=O)NC(C(O)=O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 QYELMFUTGFDVPD-UHFFFAOYSA-N 0.000 description 1
• ZELOHKZTBXXZJC-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[(4-thiophen-2-ylphenyl)sulfonylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C(C=2SC=CC=2)C=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 ZELOHKZTBXXZJC-UHFFFAOYSA-N 0.000 description 1
• BZPLJKHZMRMAFU-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]-2-[[3-(trifluoromethyl)phenyl]sulfonylamino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=CC(C(F)(F)F)=CC=1S(=O)(=O)NC(C(=O)O)CNC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 BZPLJKHZMRMAFU-UHFFFAOYSA-N 0.000 description 1
• DDWWMUUPQVAAAD-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]butanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NC(CC(O)=O)C)CCC1CCNCC1 DDWWMUUPQVAAAD-UHFFFAOYSA-N 0.000 description 1
• QYTQVZLPUJLGEO-UHFFFAOYSA-N 3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)NCC(=O)NCCC(=O)O)CCC1CCNCC1 QYTQVZLPUJLGEO-UHFFFAOYSA-N 0.000 description 1
• QMSUBJNIWWJREQ-UHFFFAOYSA-N 3-[[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]butanoyl]amino]butanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NC(CC(O)=O)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 QMSUBJNIWWJREQ-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• GPKDGVXBXQTHRY-UHFFFAOYSA-N 3-chloropropane-1-sulfonyl chloride Chemical compound ClCCCS(Cl)(=O)=O GPKDGVXBXQTHRY-UHFFFAOYSA-N 0.000 description 1
• KFPMLWUKHQMEBU-UHFFFAOYSA-N 3-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC(S(Cl)(=O)=O)=C1 KFPMLWUKHQMEBU-UHFFFAOYSA-N 0.000 description 1
• MWWNNNAOGWPTQY-UHFFFAOYSA-N 3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1 MWWNNNAOGWPTQY-UHFFFAOYSA-N 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• GGRUAIHRPJSYMZ-UHFFFAOYSA-N 4-(furan-2-yl)benzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=CO1 GGRUAIHRPJSYMZ-UHFFFAOYSA-N 0.000 description 1
• OZDCZHDOIBUGAJ-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)C=C1 OZDCZHDOIBUGAJ-UHFFFAOYSA-N 0.000 description 1
• ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
• IWWVSFPGXLWBPN-UHFFFAOYSA-N 4-chloronaphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(Cl)=CC=C(S(Cl)(=O)=O)C2=C1 IWWVSFPGXLWBPN-UHFFFAOYSA-N 0.000 description 1
• CREMYEDHKUWVTB-UHFFFAOYSA-N 4-cyclohexylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1CCCCC1 CREMYEDHKUWVTB-UHFFFAOYSA-N 0.000 description 1
• KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical compound C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 description 1
• BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 1
• QEFYRYVTYJSUJE-UHFFFAOYSA-N 4-fluoronaphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(F)=CC=C(S(Cl)(=O)=O)C2=C1 QEFYRYVTYJSUJE-UHFFFAOYSA-N 0.000 description 1
• DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 1
• AEUOWSIJWYQOJG-UHFFFAOYSA-N 4-methoxynaphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(OC)=CC=C(S(Cl)(=O)=O)C2=C1 AEUOWSIJWYQOJG-UHFFFAOYSA-N 0.000 description 1
• TYJOQICPGZGYDT-UHFFFAOYSA-N 4-methylsulfonylbenzenesulfonyl chloride Chemical compound CS(=O)(=O)C1=CC=C(S(Cl)(=O)=O)C=C1 TYJOQICPGZGYDT-UHFFFAOYSA-N 0.000 description 1
• ALBQXDHCMLLQMB-UHFFFAOYSA-N 4-phenylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=CC=C1 ALBQXDHCMLLQMB-UHFFFAOYSA-N 0.000 description 1
• BZZMNNZVMKQFED-UHFFFAOYSA-N 4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(C(=O)O)CCC1CCNCC1 BZZMNNZVMKQFED-UHFFFAOYSA-N 0.000 description 1
• LEFGAGRZHLNPLS-UHFFFAOYSA-N 4-propylbenzenesulfonyl chloride Chemical compound CCCC1=CC=C(S(Cl)(=O)=O)C=C1 LEFGAGRZHLNPLS-UHFFFAOYSA-N 0.000 description 1
• IRDZCMUQNGEQEP-UHFFFAOYSA-N 4-thiophen-2-ylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=CS1 IRDZCMUQNGEQEP-UHFFFAOYSA-N 0.000 description 1
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
• NZDZQWZJQYKDBC-UHFFFAOYSA-N 5-bromo-2-prop-2-ynoxybenzaldehyde Chemical compound BrC1=CC=C(OCC#C)C(C=O)=C1 NZDZQWZJQYKDBC-UHFFFAOYSA-N 0.000 description 1
• CSHLBIAVPAYYSH-UHFFFAOYSA-N 5-phenyl-3-[[2-[[4-piperidin-4-yl-2-(2-piperidin-4-ylethyl)butanoyl]amino]acetyl]amino]pentanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CCC(CCC1CCNCC1)C(=O)NCC(=O)NC(CC(=O)O)CCC1=CC=CC=C1 CSHLBIAVPAYYSH-UHFFFAOYSA-N 0.000 description 1
• WTUCGFYIXJREBR-UHFFFAOYSA-N 6,7-dimethoxynaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2C=C(OC)C(OC)=CC2=C1 WTUCGFYIXJREBR-UHFFFAOYSA-N 0.000 description 1
• QYCDJXYAIDWYFK-UHFFFAOYSA-N 6-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=CC(OC)=CC=C21 QYCDJXYAIDWYFK-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• KYJUGYHMMCDUIC-UMSFTDKQSA-N C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC[C@@H](C(=O)OCC)NS(=O)(=O)C1=C(C=C(C=C1C)C)C Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC[C@@H](C(=O)OCC)NS(=O)(=O)C1=C(C=C(C=C1C)C)C KYJUGYHMMCDUIC-UMSFTDKQSA-N 0.000 description 1
• BZQRHZZOFBALBE-LJAQVGFWSA-N C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC[C@@H](C(=O)OCC)NS(=O)(=O)C=1SC=CC=1 Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC[C@@H](C(=O)OCC)NS(=O)(=O)C=1SC=CC=1 BZQRHZZOFBALBE-LJAQVGFWSA-N 0.000 description 1
• LEEXWKRULOUGOX-UMSFTDKQSA-N C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(NCCC(NC[C@H](NC(OCC1=CC=CC=C1)=O)C(=O)OCC)=O)=O Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(NCCC(NC[C@H](NC(OCC1=CC=CC=C1)=O)C(=O)OCC)=O)=O LEEXWKRULOUGOX-UMSFTDKQSA-N 0.000 description 1
• CMGSQAQTWSBPFL-PMERELPUSA-N CCCCS(=O)(=O)N[C@@H](CNC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)OCC Chemical compound CCCCS(=O)(=O)N[C@@H](CNC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)OCC CMGSQAQTWSBPFL-PMERELPUSA-N 0.000 description 1
• QCGOWPWMRUILNI-BHVANESWSA-N CCOC(=O)[C@H](CNC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(CC1)C(=O)OC(C)(C)C)NS(=O)(=O)c1ccc2ccccc2c1 Chemical compound CCOC(=O)[C@H](CNC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(CC1)C(=O)OC(C)(C)C)NS(=O)(=O)c1ccc2ccccc2c1 QCGOWPWMRUILNI-BHVANESWSA-N 0.000 description 1
• 108010083161 CRL 42796 Proteins 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• VBDQGZGFNAQIIQ-ARIINYJRSA-N Cl.Cl.C([C@@H](C(=O)OCC)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 Chemical compound Cl.Cl.C([C@@H](C(=O)OCC)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)NC(=O)CNC(=O)C(CCC1CCNCC1)CCC1CCNCC1 VBDQGZGFNAQIIQ-ARIINYJRSA-N 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 229940127007 Compound 39 Drugs 0.000 description 1
• XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
• 102000009123 Fibrin Human genes 0.000 description 1
• 108010073385 Fibrin Proteins 0.000 description 1
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 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
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• ROEFLTMKUJXZGZ-FERBBOLQSA-N OC(=O)C(F)(F)F.C([C@H](N)C(=O)NCCC=1C=2C=CNC=2C=CC=1)C(=O)OCC1=CC=CC=C1 Chemical compound OC(=O)C(F)(F)F.C([C@H](N)C(=O)NCCC=1C=2C=CNC=2C=CC=1)C(=O)OCC1=CC=CC=C1 ROEFLTMKUJXZGZ-FERBBOLQSA-N 0.000 description 1
• SUDGAIBNUOBLPS-RSAXXLAASA-N OC(=O)C(F)(F)F.CC(C)C(C(C)C)NC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 Chemical compound OC(=O)C(F)(F)F.CC(C)C(C(C)C)NC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 SUDGAIBNUOBLPS-RSAXXLAASA-N 0.000 description 1
• PTQLDDYARSLQIL-FERBBOLQSA-N OC(=O)C(F)(F)F.COC1=CC=CC(CCNC(=O)[C@@H](N)CC(=O)OCC=2C=CC=CC=2)=C1 Chemical compound OC(=O)C(F)(F)F.COC1=CC=CC(CCNC(=O)[C@@H](N)CC(=O)OCC=2C=CC=CC=2)=C1 PTQLDDYARSLQIL-FERBBOLQSA-N 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000002744 anti-aggregatory effect Effects 0.000 description 1
• 230000002785 anti-thrombosis Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 230000008321 arterial blood flow Effects 0.000 description 1
• UTCFIXNJGRPEDG-RSAXXLAASA-N benzyl (3S)-3-amino-4-(1,3-benzodioxol-5-ylmethylamino)-4-oxobutanoate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](N)C(=O)NCC=1C=C2OCOC2=CC=1)C(=O)OCC1=CC=CC=C1 UTCFIXNJGRPEDG-RSAXXLAASA-N 0.000 description 1
• FLFRTMGPGGPOLP-BOXHHOBZSA-N benzyl (3S)-3-amino-4-(4-benzylpiperidin-1-yl)-4-oxobutanoate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](N)C(=O)N1CCC(CC=2C=CC=CC=2)CC1)C(=O)OCC1=CC=CC=C1 FLFRTMGPGGPOLP-BOXHHOBZSA-N 0.000 description 1
• QWVXCCLATHKNRB-FERBBOLQSA-N benzyl (3S)-3-amino-4-[2-(4-methoxyphenyl)ethylamino]-4-oxobutanoate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(OC)=CC=C1CCNC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 QWVXCCLATHKNRB-FERBBOLQSA-N 0.000 description 1
• AKYIJWOGUYDQNG-FERBBOLQSA-N benzyl (3S)-3-amino-4-oxo-4-(3-phenylpropylamino)butanoate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](N)C(=O)NCCCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 AKYIJWOGUYDQNG-FERBBOLQSA-N 0.000 description 1
• JNQKNEPKQKBXMO-KPEITVJRSA-N benzyl (3S)-4-(1-adamantylamino)-3-amino-4-oxobutanoate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](N)C(=O)NC12CC3CC(CC(C3)C1)C2)C(=O)OCC1=CC=CC=C1 JNQKNEPKQKBXMO-KPEITVJRSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 238000005842 biochemical reaction Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 230000023555 blood coagulation Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
• 238000007675 cardiac surgery Methods 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 230000015271 coagulation Effects 0.000 description 1
• 238000005345 coagulation Methods 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125810 compound 20 Drugs 0.000 description 1
• 229940125878 compound 36 Drugs 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 229940125844 compound 46 Drugs 0.000 description 1
• VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• NPZRMFLCHJTYDX-UHFFFAOYSA-N ethyl 3-(2-aminopropanoylamino)-2-(naphthalen-2-ylsulfonylamino)propanoate;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(S(=O)(=O)NC(CNC(=O)C(C)N)C(=O)OCC)=CC=C21 NPZRMFLCHJTYDX-UHFFFAOYSA-N 0.000 description 1
• CEXQHLRJVYXXCZ-UHFFFAOYSA-N ethyl 3-[(2-amino-2-phenylacetyl)amino]-2-(naphthalen-2-ylsulfonylamino)propanoate;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(=O)OCC)CNC(=O)C(N)C1=CC=CC=C1 CEXQHLRJVYXXCZ-UHFFFAOYSA-N 0.000 description 1
• ZBYOMUUGERJLLS-UHFFFAOYSA-N ethyl 3-amino-2-(1,3-benzothiazol-2-ylsulfonylamino)propanoate;hydrochloride Chemical compound Cl.C1=CC=C2SC(S(=O)(=O)NC(CN)C(=O)OCC)=NC2=C1 ZBYOMUUGERJLLS-UHFFFAOYSA-N 0.000 description 1
• ZMLSQJTUIWUTMQ-UHFFFAOYSA-N ethyl 3-amino-2-(propan-2-ylsulfonylamino)propanoate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)C(CN)NS(=O)(=O)C(C)C ZMLSQJTUIWUTMQ-UHFFFAOYSA-N 0.000 description 1
• NKQHQIJWIYNEIX-UHFFFAOYSA-N ethyl 3-amino-3-(1,3-benzodioxol-5-yl)propanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=C2OCOC2=C1 NKQHQIJWIYNEIX-UHFFFAOYSA-N 0.000 description 1
• KSTQMGKTDCXEPV-UHFFFAOYSA-N ethyl 3-amino-3-(2,3-dihydro-1,4-benzodioxin-6-yl)propanoate;hydrochloride Chemical compound Cl.O1CCOC2=CC(C(N)CC(=O)OCC)=CC=C21 KSTQMGKTDCXEPV-UHFFFAOYSA-N 0.000 description 1
• APXOQZLYYZROMW-UHFFFAOYSA-N ethyl 3-amino-3-(3,4-dimethoxyphenyl)propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=C(OC)C(OC)=C1 APXOQZLYYZROMW-UHFFFAOYSA-N 0.000 description 1
• HGZKHFJFAHULCP-UHFFFAOYSA-N ethyl 3-amino-3-(3-methoxyphenyl)propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=CC(OC)=C1 HGZKHFJFAHULCP-UHFFFAOYSA-N 0.000 description 1
• DVFQZDPNVWTMNK-UHFFFAOYSA-N ethyl 3-amino-3-(4-methoxyphenyl)propanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=C(OC)C=C1 DVFQZDPNVWTMNK-UHFFFAOYSA-N 0.000 description 1
• QTVUCHOUZICCRB-UHFFFAOYSA-N ethyl 3-amino-3-(4-propan-2-ylphenyl)propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=C(C(C)C)C=C1 QTVUCHOUZICCRB-UHFFFAOYSA-N 0.000 description 1
• NYJIPZLBDYZOSO-UHFFFAOYSA-N ethyl 3-amino-3-[3-(2-ethoxy-2-oxoethoxy)phenyl]propanoate;hydrochloride Chemical compound Cl.CCOC(=O)COC1=CC=CC(C(N)CC(=O)OCC)=C1 NYJIPZLBDYZOSO-UHFFFAOYSA-N 0.000 description 1
• ATSZQDTVNRNXKB-UHFFFAOYSA-N ethyl 3-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=CC=C1 ATSZQDTVNRNXKB-UHFFFAOYSA-N 0.000 description 1
• GGANVLPLTUQZIF-UHFFFAOYSA-N ethyl 3-amino-3-pyridin-3-ylpropanoate;dihydrochloride Chemical compound Cl.Cl.CCOC(=O)CC(N)C1=CC=CN=C1 GGANVLPLTUQZIF-UHFFFAOYSA-N 0.000 description 1
• NMUSXIMXVQNKBA-UHFFFAOYSA-N ethyl 3-amino-5-phenylpentanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)CCC1=CC=CC=C1 NMUSXIMXVQNKBA-UHFFFAOYSA-N 0.000 description 1
• HHIOOBJZIASBFF-UHFFFAOYSA-N ethyl 3-aminobutanoate Chemical compound CCOC(=O)CC(C)N HHIOOBJZIASBFF-UHFFFAOYSA-N 0.000 description 1
• ISVBSAIYXBEVSI-UHFFFAOYSA-N ethyl 3-aminobutanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(C)N ISVBSAIYXBEVSI-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 208000000283 familial pityriasis rubra pilaris Diseases 0.000 description 1
• 229950003499 fibrin Drugs 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• WVKIFIROCHIWAY-UHFFFAOYSA-N hydron;2-(methylamino)acetic acid;chloride Chemical compound Cl.CNCC(O)=O WVKIFIROCHIWAY-UHFFFAOYSA-N 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 229940127554 medical product Drugs 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• OSDPSOBLGQUCQX-UHFFFAOYSA-N methyl 2,2,3,3,4,4,5,5,5-nonafluoropentanoate Chemical compound COC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F OSDPSOBLGQUCQX-UHFFFAOYSA-N 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• PJHVZZODQMXUDU-UHFFFAOYSA-N naphthalen-2-ylmethanesulfonyl chloride Chemical compound C1=CC=CC2=CC(CS(=O)(=O)Cl)=CC=C21 PJHVZZODQMXUDU-UHFFFAOYSA-N 0.000 description 1
• DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• CDRNYKLYADJTMN-UHFFFAOYSA-N pyridine-3-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CN=C1 CDRNYKLYADJTMN-UHFFFAOYSA-N 0.000 description 1
• JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
• 239000012429 reaction media Substances 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 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 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• KSWVWYUJLVFBBU-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[(1-ethoxy-1-oxo-4-phenylpentan-3-yl)amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC(CC(=O)OCC)C(C)C1=CC=CC=C1 KSWVWYUJLVFBBU-UHFFFAOYSA-N 0.000 description 1
• JAJFVGDXRFFMFO-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[(3-ethoxy-3-oxopropyl)amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NCC(=O)NCCC(=O)OCC)CCC1CCN(C(=O)OC(C)(C)C)CC1 JAJFVGDXRFFMFO-UHFFFAOYSA-N 0.000 description 1
• GDXBOTOJRSVQQS-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[(4-ethoxy-4-oxobutan-2-yl)amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NCC(=O)NC(C)CC(=O)OCC)CCC1CCN(C(=O)OC(C)(C)C)CC1 GDXBOTOJRSVQQS-UHFFFAOYSA-N 0.000 description 1
• SHFGWSHWLPAGGV-YTTGMZPUSA-N tert-butyl 4-[3-[[2-[[(2S)-2-(benzenesulfonamido)-3-ethoxy-3-oxopropyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)NCC(=O)NC[C@@H](C(=O)OCC)NS(=O)(=O)C1=CC=CC=C1 SHFGWSHWLPAGGV-YTTGMZPUSA-N 0.000 description 1
• OUIZXIMLXQFNDJ-XIFFEERXSA-N tert-butyl 4-[3-[[2-[[(2S)-3-ethoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)CCC(CCC1CCN(CC1)C(=O)OC(C)(C)C)C(NCC(NC[C@H](NC(OCC1=CC=CC=C1)=O)C(=O)OCC)=O)=O OUIZXIMLXQFNDJ-XIFFEERXSA-N 0.000 description 1
• ZYWADCKZHQHRCI-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[1-(3,4-dimethoxyphenyl)-3-ethoxy-3-oxopropyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C=1C=C(OC)C(OC)=CC=1C(CC(=O)OCC)NC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 ZYWADCKZHQHRCI-UHFFFAOYSA-N 0.000 description 1
• YMRKGSXOVKSEBV-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[2-(cyclohexylsulfonylamino)-3-methoxy-3-oxopropyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C1CCCCC1S(=O)(=O)NC(C(=O)OC)CNC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 YMRKGSXOVKSEBV-UHFFFAOYSA-N 0.000 description 1
• XGVFROFWRQKTCL-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[3-ethoxy-1-(4-methoxyphenyl)-3-oxopropyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C=1C=C(OC)C=CC=1C(CC(=O)OCC)NC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 XGVFROFWRQKTCL-UHFFFAOYSA-N 0.000 description 1
• YHFREUIMWUNYJW-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[3-ethoxy-1-[3-(2-ethoxy-2-oxoethoxy)phenyl]-3-oxopropyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound CCOC(=O)COC1=CC=CC(C(CC(=O)OCC)NC(=O)CNC(=O)C(CCC2CCN(CC2)C(=O)OC(C)(C)C)CCC2CCN(CC2)C(=O)OC(C)(C)C)=C1 YHFREUIMWUNYJW-UHFFFAOYSA-N 0.000 description 1
• JQBGCGLZQXKXKT-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[3-ethoxy-3-oxo-1-(4-propan-2-ylphenyl)propyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C=1C=C(C(C)C)C=CC=1C(CC(=O)OCC)NC(=O)CNC(=O)C(CCC1CCN(CC1)C(=O)OC(C)(C)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 JQBGCGLZQXKXKT-UHFFFAOYSA-N 0.000 description 1
• RACJHWGKSBJEOC-UHFFFAOYSA-N tert-butyl 4-[3-[[2-[[3-ethoxy-3-oxo-2-(propan-2-ylsulfonylamino)propyl]amino]-2-oxoethyl]carbamoyl]-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pentyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(C(=O)NCC(=O)NCC(C(=O)OCC)NS(=O)(=O)C(C)C)CCC1CCN(C(=O)OC(C)(C)C)CC1 RACJHWGKSBJEOC-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
• 229940038773 trisodium citrate Drugs 0.000 description 1
• 231100000216 vascular lesion Toxicity 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1