AU2003285336B2 - Imidazole-derivatives as factor Xa inhibitors - Google Patents

Info

Publication number

AU2003285336B2

AU2003285336B2 AU2003285336A AU2003285336A AU2003285336B2 AU 2003285336 B2 AU2003285336 B2 AU 2003285336B2 AU 2003285336 A AU2003285336 A AU 2003285336A AU 2003285336 A AU2003285336 A AU 2003285336A AU 2003285336 B2 AU2003285336 B2 AU 2003285336B2

Authority

AU

Australia

Prior art keywords

chloro

imidazole

ylmethyl

isopropyl

thiophen

Prior art date

2002-12-04

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title description 5
• 229940123583 Factor Xa inhibitor Drugs 0.000 title description 2
• -1 (C 2 -C 4 )-alkyl Chemical group 0.000 claims description 322
• 150000001875 compounds Chemical class 0.000 claims description 202
• 125000000623 heterocyclic group Chemical group 0.000 claims description 104
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 99
• 239000000203 mixture Substances 0.000 claims description 83
• 238000000034 method Methods 0.000 claims description 78
• 125000000217 alkyl group Chemical group 0.000 claims description 77
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 77
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 65
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 64
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 61
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 61
• 150000003839 salts Chemical class 0.000 claims description 47
• 125000004122 cyclic group Chemical group 0.000 claims description 45
• 229910052757 nitrogen Inorganic materials 0.000 claims description 44
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 40
• 108010074860 Factor Xa Proteins 0.000 claims description 37
• ZRQQXFMGYSOKDF-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine Chemical compound CC(C)N1CCC(N)CC1 ZRQQXFMGYSOKDF-UHFFFAOYSA-N 0.000 claims description 36
• 125000004076 pyridyl group Chemical group 0.000 claims description 32
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
• 230000015572 biosynthetic process Effects 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 125000001544 thienyl group Chemical group 0.000 claims description 29
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 28
• 239000000460 chlorine Substances 0.000 claims description 28
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
• 125000002883 imidazolyl group Chemical group 0.000 claims description 28
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 26
• 229910052801 chlorine Inorganic materials 0.000 claims description 25
• 239000002253 acid Substances 0.000 claims description 24
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 24
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 23
• 229910052731 fluorine Inorganic materials 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 22
• 230000005764 inhibitory process Effects 0.000 claims description 22
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 22
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 20
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 20
• 125000000335 thiazolyl group Chemical group 0.000 claims description 20
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 19
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 19
• 239000011737 fluorine Substances 0.000 claims description 17
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 17
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
• 125000000524 functional group Chemical group 0.000 claims description 15
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 15
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims description 14
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 14
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
• 229910052740 iodine Inorganic materials 0.000 claims description 13
• 238000011321 prophylaxis Methods 0.000 claims description 13
• 208000007536 Thrombosis Diseases 0.000 claims description 12
• 229910052794 bromium Inorganic materials 0.000 claims description 12
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
• 238000002560 therapeutic procedure Methods 0.000 claims description 12
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 11
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
• 230000023555 blood coagulation Effects 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• 238000002360 preparation method Methods 0.000 claims description 11
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
• YWHRLNVUUYDTFM-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-2,4-dicarboxylic acid Chemical compound OC(=O)C1=NC(C(=O)O)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 YWHRLNVUUYDTFM-UHFFFAOYSA-N 0.000 claims description 9
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 9
• 239000002243 precursor Substances 0.000 claims description 9
• NKWCGTOZTHZDHB-UHFFFAOYSA-N 1h-imidazol-1-ium-4-carboxylate Chemical compound OC(=O)C1=CNC=N1 NKWCGTOZTHZDHB-UHFFFAOYSA-N 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 8
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 125000002757 morpholinyl group Chemical group 0.000 claims description 8
• JXNUZOZNXLOXIO-UHFFFAOYSA-N tert-butyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]imidazole-4-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C(=O)OC(C)(C)C)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 JXNUZOZNXLOXIO-UHFFFAOYSA-N 0.000 claims description 8
• 238000011282 treatment Methods 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 7
• 239000003146 anticoagulant agent Substances 0.000 claims description 7
• 208000037803 restenosis Diseases 0.000 claims description 7
• 238000001356 surgical procedure Methods 0.000 claims description 7
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
• 230000002792 vascular Effects 0.000 claims description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
• WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 claims description 6
• 125000002843 carboxylic acid group Chemical group 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 230000020764 fibrinolysis Effects 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
• 210000003462 vein Anatomy 0.000 claims description 6
• 208000001435 Thromboembolism Diseases 0.000 claims description 5
• 230000001154 acute effect Effects 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
• 239000005977 Ethylene Substances 0.000 claims description 4
• 230000003187 abdominal effect Effects 0.000 claims description 4
• 238000002399 angioplasty Methods 0.000 claims description 4
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 4
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 4
• 210000003127 knee Anatomy 0.000 claims description 4
• 230000001575 pathological effect Effects 0.000 claims description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• 230000002537 thrombolytic effect Effects 0.000 claims description 4
• JVTMDVFGRFFOOB-UHFFFAOYSA-N (1-pyridin-4-ylpiperidin-4-yl)methanamine Chemical compound C1CC(CN)CCN1C1=CC=NC=C1 JVTMDVFGRFFOOB-UHFFFAOYSA-N 0.000 claims description 3
• SQVVCRRVWCTPNH-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-2-phenyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(C=2C=CC=CC=2)=N1 SQVVCRRVWCTPNH-UHFFFAOYSA-N 0.000 claims description 3
• 206010002388 Angina unstable Diseases 0.000 claims description 3
• 206010053567 Coagulopathies Diseases 0.000 claims description 3
• 208000007814 Unstable Angina Diseases 0.000 claims description 3
• 230000002159 abnormal effect Effects 0.000 claims description 3
• 206010000891 acute myocardial infarction Diseases 0.000 claims description 3
• 125000003725 azepanyl group Chemical group 0.000 claims description 3
• 208000035475 disorder Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 3
• 210000003141 lower extremity Anatomy 0.000 claims description 3
• 150000004702 methyl esters Chemical class 0.000 claims description 3
• 125000004928 piperidonyl group Chemical group 0.000 claims description 3
• PWWBZUPMYRIVAY-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(2-methyl-1,3-thiazol-4-yl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N=C1C=2N=C(C)SC=2)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 PWWBZUPMYRIVAY-UHFFFAOYSA-N 0.000 claims description 2
• FSJQSUPJONDYJO-UHFFFAOYSA-N 2-bromo-1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(Br)=N1 FSJQSUPJONDYJO-UHFFFAOYSA-N 0.000 claims description 2
• UZTYWUGPXUBCFJ-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methylimidazole-2,4-dicarboxylic acid Chemical compound OC(=O)C1=C(C)N=C(C(O)=O)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 UZTYWUGPXUBCFJ-UHFFFAOYSA-N 0.000 claims description 2
• ZIMGEXAUEBWXES-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-2-pyridin-3-ylimidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1=CC=CN=C1 ZIMGEXAUEBWXES-UHFFFAOYSA-N 0.000 claims description 2
• YBNNHNOBCHGYFC-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-4-carboxylic acid Chemical compound OC(=O)C1=CN=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 YBNNHNOBCHGYFC-UHFFFAOYSA-N 0.000 claims description 2
• 206010002383 Angina Pectoris Diseases 0.000 claims description 2
• 208000005189 Embolism Diseases 0.000 claims description 2
• 206010022562 Intermittent claudication Diseases 0.000 claims description 2
• 208000034486 Multi-organ failure Diseases 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
• 206010040070 Septic Shock Diseases 0.000 claims description 2
• 206010047249 Venous thrombosis Diseases 0.000 claims description 2
• 208000036142 Viral infection Diseases 0.000 claims description 2
• 210000001367 artery Anatomy 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 238000007887 coronary angioplasty Methods 0.000 claims description 2
• 208000029078 coronary artery disease Diseases 0.000 claims description 2
• 238000001631 haemodialysis Methods 0.000 claims description 2
• 230000000322 hemodialysis Effects 0.000 claims description 2
• 230000028709 inflammatory response Effects 0.000 claims description 2
• 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
• 230000007774 longterm Effects 0.000 claims description 2
• 238000012423 maintenance Methods 0.000 claims description 2
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 230000002093 peripheral effect Effects 0.000 claims description 2
• 238000010577 post-coronary angioplasty Methods 0.000 claims description 2
• 230000036303 septic shock Effects 0.000 claims description 2
• 230000009885 systemic effect Effects 0.000 claims description 2
• 238000007891 venous angioplasty Methods 0.000 claims description 2
• 230000009385 viral infection Effects 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• VFESBYCZOFMEOU-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-cyclopropylimidazole-4-carboxylic acid Chemical compound C1CC1C1=NC(C(=O)O)=CN1CC(=NO1)C=C1C1=CC=C(Cl)S1 VFESBYCZOFMEOU-UHFFFAOYSA-N 0.000 claims 1
• FATYCSGOMDMDSG-UHFFFAOYSA-N 2-bromo-3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N=C(Br)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 FATYCSGOMDMDSG-UHFFFAOYSA-N 0.000 claims 1
• SSVVQWPFIYZSMB-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(2-methoxyphenyl)-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound COC1=CC=CC=C1C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=NC(C)=C1C(=O)NC1CCN(C(C)C)CC1 SSVVQWPFIYZSMB-UHFFFAOYSA-N 0.000 claims 1
• GBRSKSQHVWDKRZ-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-2-[3-(trifluoromethyl)phenyl]imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1=CC=CC(C(F)(F)F)=C1 GBRSKSQHVWDKRZ-UHFFFAOYSA-N 0.000 claims 1
• 206010038687 Respiratory distress Diseases 0.000 claims 1
• FJLNULNJIBLGSV-UHFFFAOYSA-N [2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl] 1H-imidazole-5-carboxylate Chemical compound CC(C)(C)OC(=O)COC(=O)C1=CNC=N1 FJLNULNJIBLGSV-UHFFFAOYSA-N 0.000 claims 1
• 229940125898 compound 5 Drugs 0.000 claims 1
• CTOMUGSXTMGVGB-UHFFFAOYSA-N ethyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]imidazole-2-carboxylate Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(C(=O)OCC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 CTOMUGSXTMGVGB-UHFFFAOYSA-N 0.000 claims 1
• 230000000302 ischemic effect Effects 0.000 claims 1
• BVSZRCIAEUHGJW-UHFFFAOYSA-N methyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]imidazole-4-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C(=O)OC)=CN1CC(=NO1)C=C1C1=CC=C(Cl)S1 BVSZRCIAEUHGJW-UHFFFAOYSA-N 0.000 claims 1
• 208000011580 syndromic disease Diseases 0.000 claims 1
• 230000001052 transient effect Effects 0.000 claims 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 97
• 239000000243 solution Substances 0.000 description 67
• 125000001309 chloro group Chemical group Cl* 0.000 description 65
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
• 125000003118 aryl group Chemical group 0.000 description 58
• 229910052736 halogen Inorganic materials 0.000 description 51
• 150000002367 halogens Chemical class 0.000 description 51
• 238000006243 chemical reaction Methods 0.000 description 48
• 230000002829 reductive effect Effects 0.000 description 47
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 45
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
• 125000002950 monocyclic group Chemical group 0.000 description 41
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 40
• 239000000047 product Substances 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 238000000746 purification Methods 0.000 description 35
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• 239000000651 prodrug Substances 0.000 description 29
• 229940002612 prodrug Drugs 0.000 description 29
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 28
• 125000002619 bicyclic group Chemical group 0.000 description 28
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 26
• 125000005842 heteroatom Chemical group 0.000 description 25
• 239000007787 solid Substances 0.000 description 25
• 238000003786 synthesis reaction Methods 0.000 description 25
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 238000004128 high performance liquid chromatography Methods 0.000 description 24
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 23
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 23
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 23
• 125000001424 substituent group Chemical group 0.000 description 23
• 238000010828 elution Methods 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 21
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 21
• 229910052717 sulfur Inorganic materials 0.000 description 21
• 239000011593 sulfur Substances 0.000 description 21
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 20
• 229940093499 ethyl acetate Drugs 0.000 description 20
• 235000019439 ethyl acetate Nutrition 0.000 description 20
• 239000001301 oxygen Substances 0.000 description 20
• 229910052760 oxygen Inorganic materials 0.000 description 20
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 19
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 19
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 19
• 230000000694 effects Effects 0.000 description 19
• 150000003536 tetrazoles Chemical class 0.000 description 19
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 18
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 18
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 18
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 18
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 18
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 18
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 18
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 18
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 18
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 17
• 125000004432 carbon atom Chemical group C* 0.000 description 17
• 238000002953 preparative HPLC Methods 0.000 description 17
• 125000004429 atom Chemical group 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 14
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 14
• 125000001041 indolyl group Chemical group 0.000 description 14
• 125000000168 pyrrolyl group Chemical group 0.000 description 14
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 description 13
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 13
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 13
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 13
• CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 12
• GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 12
• 239000003153 chemical reaction reagent Substances 0.000 description 12
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• QKPVEISEHYYHRH-UHFFFAOYSA-N 2-methoxyacetonitrile Chemical compound COCC#N QKPVEISEHYYHRH-UHFFFAOYSA-N 0.000 description 11
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 11
• BWCDLEQTELFBAW-UHFFFAOYSA-N 3h-dioxazole Chemical compound N1OOC=C1 BWCDLEQTELFBAW-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 11
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 11
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 11
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 11
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 11
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 11
• 125000002541 furyl group Chemical group 0.000 description 11
• 150000002460 imidazoles Chemical class 0.000 description 11
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 11
• 125000002971 oxazolyl group Chemical group 0.000 description 11
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 11
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 11
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 11
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 11
• 230000002441 reversible effect Effects 0.000 description 11
• 125000003831 tetrazolyl group Chemical group 0.000 description 11
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 11
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 10
• UBIXPIXAVFHKMM-UHFFFAOYSA-N 3-(bromomethyl)-5-(5-chlorothiophen-2-yl)-1,2-oxazole Chemical compound S1C(Cl)=CC=C1C1=CC(CBr)=NO1 UBIXPIXAVFHKMM-UHFFFAOYSA-N 0.000 description 10
• CBPGYUDFPXPOLZ-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[2-(2-methoxyethoxy)ethoxymethyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(COCCOCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 CBPGYUDFPXPOLZ-UHFFFAOYSA-N 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• 125000001786 isothiazolyl group Chemical group 0.000 description 10
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 10
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 10
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 10
• 125000002053 thietanyl group Chemical group 0.000 description 10
• WOSRKCGWIHPOTL-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1.C1CNCCOC1 WOSRKCGWIHPOTL-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
• 239000006227 byproduct Substances 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 8
• ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 8
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 8
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 8
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 8
• KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 8
• YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 8
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 8
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 8
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 8
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 8
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 8
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 8
• 229940088598 enzyme Drugs 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 8
• DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 7
• VLSJTEKDAFDRSE-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]imidazole-2-carboxylic acid Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(O)=O)=C1 VLSJTEKDAFDRSE-UHFFFAOYSA-N 0.000 description 7
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 7
• XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
• 125000002252 acyl group Chemical group 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 125000003971 isoxazolinyl group Chemical group 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 125000001624 naphthyl group Chemical group 0.000 description 7
• 125000004193 piperazinyl group Chemical group 0.000 description 7
• 125000003367 polycyclic group Chemical group 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 7
• 229930192474 thiophene Natural products 0.000 description 7
• IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 7
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 6
• ZHKJHQBOAJQXQR-UHFFFAOYSA-N 1H-azirine Chemical compound N1C=C1 ZHKJHQBOAJQXQR-UHFFFAOYSA-N 0.000 description 6
• SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 6
• NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 6
• ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 6
• AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 6
• KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• JZFICWYCTCCINF-UHFFFAOYSA-N Thiadiazin Chemical compound S=C1SC(C)NC(C)N1CCN1C(=S)SC(C)NC1C JZFICWYCTCCINF-UHFFFAOYSA-N 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 125000005602 azabenzimidazolyl group Chemical group 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 description 6
• OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 6
• SJGALSBBFTYSBA-UHFFFAOYSA-N oxaziridine Chemical compound C1NO1 SJGALSBBFTYSBA-UHFFFAOYSA-N 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 238000010561 standard procedure Methods 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 5
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 5
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 5
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 5
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 5
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 5
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 5
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 5
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 5
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 5
• 125000000164 1,3-thiazinyl group Chemical group S1C(N=CC=C1)* 0.000 description 5
• 125000005962 1,4-oxazepanyl group Chemical group 0.000 description 5
• 125000000183 1,4-thiazinyl group Chemical group S1C(C=NC=C1)* 0.000 description 5
• SKZUXKOWTWFPPH-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine;hydrochloride Chemical compound Cl.CC(C)N1CCC(N)CC1 SKZUXKOWTWFPPH-UHFFFAOYSA-N 0.000 description 5
• 125000005955 1H-indazolyl group Chemical group 0.000 description 5
• JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 5
• XYYIHBSYADINEC-UHFFFAOYSA-N 2-bromo-n-(5-chloropyridin-2-yl)acetamide Chemical compound ClC1=CC=C(NC(=O)CBr)N=C1 XYYIHBSYADINEC-UHFFFAOYSA-N 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 5
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 125000002015 acyclic group Chemical group 0.000 description 5
• 238000005804 alkylation reaction Methods 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 5
• 125000002785 azepinyl group Chemical group 0.000 description 5
• 125000002393 azetidinyl group Chemical group 0.000 description 5
• 125000004069 aziridinyl group Chemical group 0.000 description 5
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 5
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 5
• 125000005512 benztetrazolyl group Chemical group 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 125000004623 carbolinyl group Chemical group 0.000 description 5
• 150000001735 carboxylic acids Chemical class 0.000 description 5
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 5
• 125000003838 furazanyl group Chemical group 0.000 description 5
• KRGRHIQRVYJCIG-UHFFFAOYSA-N hydron;1-propan-2-ylpiperidin-4-amine;dichloride Chemical compound Cl.Cl.CC(C)N1CCC(N)CC1 KRGRHIQRVYJCIG-UHFFFAOYSA-N 0.000 description 5
• 125000002632 imidazolidinyl group Chemical group 0.000 description 5
• 125000002636 imidazolinyl group Chemical group 0.000 description 5
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 5
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 5
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 5
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 5
• 125000005438 isoindazolyl group Chemical group 0.000 description 5
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 5
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 5
• 125000005969 isothiazolinyl group Chemical group 0.000 description 5
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 5
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• OXUZCBDDXOMZAM-UHFFFAOYSA-N oxathiepane Chemical compound C1CCOSCC1 OXUZCBDDXOMZAM-UHFFFAOYSA-N 0.000 description 5
• 125000000160 oxazolidinyl group Chemical group 0.000 description 5
• 125000005968 oxazolinyl group Chemical group 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 5
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 5
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 5
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 5
• 125000005954 phenoxathiinyl group Chemical group 0.000 description 5
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 5
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 5
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 5
• 125000002755 pyrazolinyl group Chemical group 0.000 description 5
• 125000001422 pyrrolinyl group Chemical group 0.000 description 5
• 125000005493 quinolyl group Chemical group 0.000 description 5
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 238000006722 reduction reaction Methods 0.000 description 5
• 238000007127 saponification reaction Methods 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 5
• 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 5
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 5
• 125000001984 thiazolidinyl group Chemical group 0.000 description 5
• 125000002769 thiazolinyl group Chemical group 0.000 description 5
• PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 5
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 5
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 4
• ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 4
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 4
• QHJSEYSZSHUBFV-UHFFFAOYSA-N 3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]imidazole-4-carboxylic acid Chemical compound OC(=O)C1=CN=CN1CC(=O)NC1=CC=C(Cl)C=N1 QHJSEYSZSHUBFV-UHFFFAOYSA-N 0.000 description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 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
• JVVRFURWYLGWPG-UHFFFAOYSA-N N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazole-5-carboxamide Chemical compound C(C)(C)N1CCC(CC1)NC(=O)C=1N=CNC=1 JVVRFURWYLGWPG-UHFFFAOYSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
• 108090000190 Thrombin Proteins 0.000 description 4
• 108010000499 Thromboplastin Proteins 0.000 description 4
• 102000002262 Thromboplastin Human genes 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 125000002947 alkylene group Chemical group 0.000 description 4
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 230000015271 coagulation Effects 0.000 description 4
• 238000005345 coagulation Methods 0.000 description 4
• 238000009833 condensation Methods 0.000 description 4
• 230000005494 condensation Effects 0.000 description 4
• DIXBSCZRIZDQGC-UHFFFAOYSA-N diaziridine Chemical compound C1NN1 DIXBSCZRIZDQGC-UHFFFAOYSA-N 0.000 description 4
• VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 235000019198 oils Nutrition 0.000 description 4
• 125000004043 oxo group Chemical group O=* 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 229960004072 thrombin Drugs 0.000 description 4
• 125000001425 triazolyl group Chemical group 0.000 description 4
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 3
• RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 3
• RFOHSZFQYMEWMH-UHFFFAOYSA-N 1,3-diazocan-2-one Chemical compound O=C1NCCCCCN1 RFOHSZFQYMEWMH-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• CXPUAWQOXQINEX-UHFFFAOYSA-N 1,4-diazocane Chemical compound C1CCNCCNC1 CXPUAWQOXQINEX-UHFFFAOYSA-N 0.000 description 3
• HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical group C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 3
• GYZMNNQUSLUCLP-UHFFFAOYSA-N 1,4-dioxocane Chemical compound C1CCOCCOC1 GYZMNNQUSLUCLP-UHFFFAOYSA-N 0.000 description 3
• OLIXBQIGIJMNBA-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]imidazole Chemical compound COC1=CC=CC(CN2C=NC=C2)=C1 OLIXBQIGIJMNBA-UHFFFAOYSA-N 0.000 description 3
• VUVRSIJYSZMBSG-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 VUVRSIJYSZMBSG-UHFFFAOYSA-N 0.000 description 3
• KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 description 3
• CFNZJUUPIZLFLS-UHFFFAOYSA-N 2-[2-(2-methoxyethoxy)ethoxy]acetonitrile Chemical compound COCCOCCOCC#N CFNZJUUPIZLFLS-UHFFFAOYSA-N 0.000 description 3
• IQYQWRHUAJTQMS-UHFFFAOYSA-N 2-[2-(2-methoxyethoxy)ethoxymethyl]-n-(1-propan-2-ylpiperidin-4-yl)-1h-imidazole-5-carboxamide Chemical compound N1C(COCCOCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 IQYQWRHUAJTQMS-UHFFFAOYSA-N 0.000 description 3
• CKIMEHMDVFYYNJ-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(1,4-oxazepane-4-carbonyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C(=O)N1CCOCCC1 CKIMEHMDVFYYNJ-UHFFFAOYSA-N 0.000 description 3
• ZQPOZMLMJIOGDM-UHFFFAOYSA-N 4-o-tert-butyl 2-o-ethyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=NC=C(C(=O)OC(C)(C)C)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 ZQPOZMLMJIOGDM-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 229940127219 anticoagulant drug Drugs 0.000 description 3
• 238000006254 arylation reaction Methods 0.000 description 3
• MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
• 208000034158 bleeding Diseases 0.000 description 3
• 230000000740 bleeding effect Effects 0.000 description 3
• 239000003130 blood coagulation factor inhibitor Substances 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 125000006165 cyclic alkyl group Chemical group 0.000 description 3
• WZVHPXGAWGWKTL-UHFFFAOYSA-N diazocan-3-one Chemical compound O=C1CCCCCNN1 WZVHPXGAWGWKTL-UHFFFAOYSA-N 0.000 description 3
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 3
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
• 238000004108 freeze drying Methods 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 3
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 3
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 3
• PLCDAVKHGISMKL-UHFFFAOYSA-N methyl 2-(methoxymethyl)-1h-imidazole-5-carboxylate Chemical compound COCC1=NC=C(C(=O)OC)N1 PLCDAVKHGISMKL-UHFFFAOYSA-N 0.000 description 3
• YFEPBWKUBQUBKL-UHFFFAOYSA-N methyl 3-(1h-imidazol-5-yl)propanoate Chemical compound COC(=O)CCC1=CN=CN1 YFEPBWKUBQUBKL-UHFFFAOYSA-N 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• WBZGIUUOANPBGJ-UHFFFAOYSA-N n'-hydroxy-2-[2-(2-methoxyethoxy)ethoxy]ethanimidamide Chemical compound COCCOCCOCC(=N)NO WBZGIUUOANPBGJ-UHFFFAOYSA-N 0.000 description 3
• CZDAUXGTCCOVHY-UHFFFAOYSA-N n-(1-propan-2-ylpiperidin-4-yl)-1h-imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=CN1 CZDAUXGTCCOVHY-UHFFFAOYSA-N 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 150000003457 sulfones Chemical class 0.000 description 3
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 3
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 3
• 229910052723 transition metal Inorganic materials 0.000 description 3
• 150000003624 transition metals Chemical class 0.000 description 3
• IYCMYOWBZQNVBV-UHFFFAOYSA-N (1-propan-2-ylpiperidin-4-yl)methanamine Chemical compound CC(C)N1CCC(CN)CC1 IYCMYOWBZQNVBV-UHFFFAOYSA-N 0.000 description 2
• 125000006565 (C4-C7) cyclic group Chemical group 0.000 description 2
• MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 2
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• AWCLWIBIPNQHCV-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1CC1=CC=CC(F)=C1 AWCLWIBIPNQHCV-UHFFFAOYSA-N 0.000 description 2
• CJPDUWXKEBWEEX-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-n-(1-pyridin-4-ylazetidin-3-yl)imidazole-2-carboxamide Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(=O)NC2CN(C2)C=2C=CN=CC=2)=C1 CJPDUWXKEBWEEX-UHFFFAOYSA-N 0.000 description 2
• OJXHKGYIAREDER-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-n-(1-pyridin-4-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(=O)NC2CCN(CC2)C=2C=CN=CC=2)=C1 OJXHKGYIAREDER-UHFFFAOYSA-N 0.000 description 2
• KEHXZSQTJGGEHG-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-n-[(1-pyridin-4-ylpiperidin-4-yl)methyl]imidazole-2-carboxamide Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(=O)NCC2CCN(CC2)C=2C=CN=CC=2)=C1 KEHXZSQTJGGEHG-UHFFFAOYSA-N 0.000 description 2
• HETGMVMKSOFEGV-UHFFFAOYSA-N 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-ethylsulfonyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound CCS(=O)(=O)C1=NC(C(=O)NC2CCN(CC2)C(C)C)=CN1CC(=O)NC1=CC=C(Cl)C=N1 HETGMVMKSOFEGV-UHFFFAOYSA-N 0.000 description 2
• YYHKQPYEOPTBFQ-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]imidazole-4-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C(O)=O)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 YYHKQPYEOPTBFQ-UHFFFAOYSA-N 0.000 description 2
• YXOUGNRWMCOIRT-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-iodo-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(I)=N1 YXOUGNRWMCOIRT-UHFFFAOYSA-N 0.000 description 2
• PDJVKETXXQUAHN-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-pyridin-4-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound S1C(Cl)=CC=C1C1=CC(CN2C(=NC=C2)C(=O)NC2CCN(CC2)C=2C=CN=CC=2)=NO1 PDJVKETXXQUAHN-UHFFFAOYSA-N 0.000 description 2
• HEZDROBBYQPLCQ-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-[(1-propan-2-ylazetidin-3-yl)methyl]imidazole-2-carboxamide Chemical compound C1N(C(C)C)CC1CNC(=O)C1=NC=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 HEZDROBBYQPLCQ-UHFFFAOYSA-N 0.000 description 2
• RRYVASUWSSVCJI-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-[(1-propan-2-ylpiperidin-4-yl)methyl]imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1CNC(=O)C1=NC=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 RRYVASUWSSVCJI-UHFFFAOYSA-N 0.000 description 2
• ZVNQSGYKXMUAKJ-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-[(1-pyridin-4-ylpiperidin-4-yl)methyl]imidazole-2-carboxamide Chemical compound S1C(Cl)=CC=C1C1=CC(CN2C(=NC=C2)C(=O)NCC2CCN(CC2)C=2C=CN=CC=2)=NO1 ZVNQSGYKXMUAKJ-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• KMXUKZCMNKLUTF-UHFFFAOYSA-N 1-chloro-4-(2-chloroethyl)benzene Chemical compound ClCCC1=CC=C(Cl)C=C1 KMXUKZCMNKLUTF-UHFFFAOYSA-N 0.000 description 2
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
• BTDZSVPICJLNIN-UHFFFAOYSA-N 1-pyridin-4-ylpiperidin-4-amine Chemical compound C1CC(N)CCN1C1=CC=NC=C1 BTDZSVPICJLNIN-UHFFFAOYSA-N 0.000 description 2
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 2
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 2
• VKJBICQSBBONRC-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-azocin-8-one Chemical compound O=C1NCCCCC=C1 VKJBICQSBBONRC-UHFFFAOYSA-N 0.000 description 2
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
• DAGAJDMREYYCOG-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N=C1C=2C=CC(Cl)=CC=2)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 DAGAJDMREYYCOG-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• OWJHDLWPHIGCIB-UHFFFAOYSA-N 3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-(2-methoxyethoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C=1C=C(Cl)C=NC=1NC(=O)CN1C(COCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 OWJHDLWPHIGCIB-UHFFFAOYSA-N 0.000 description 2
• FHKKZQRMEGCAFW-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(2,6-dichlorophenyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1=C(Cl)C=CC=C1Cl FHKKZQRMEGCAFW-UHFFFAOYSA-N 0.000 description 2
• JXTSGAGKZUBVSP-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(2-methoxyethoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(COCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 JXTSGAGKZUBVSP-UHFFFAOYSA-N 0.000 description 2
• AGZZSSXJFDUCPY-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(methoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(COC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 AGZZSSXJFDUCPY-UHFFFAOYSA-N 0.000 description 2
• XCIQCFHPYXRIGV-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-iodo-5-methylimidazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)N=C(I)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 XCIQCFHPYXRIGV-UHFFFAOYSA-N 0.000 description 2
• RMCRXKQDYFVULZ-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-2-phenyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=C(C)N=C1C1=CC=CC=C1 RMCRXKQDYFVULZ-UHFFFAOYSA-N 0.000 description 2
• DUHWJKMRMPOBCR-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=CN=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 DUHWJKMRMPOBCR-UHFFFAOYSA-N 0.000 description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• NQDDAIWQYADLDC-UHFFFAOYSA-N 5-(5-chlorothiophen-2-yl)-3-(imidazol-1-ylmethyl)-1,2-oxazole Chemical compound S1C(Cl)=CC=C1C1=CC(CN2C=NC=C2)=NO1 NQDDAIWQYADLDC-UHFFFAOYSA-N 0.000 description 2
• ICJSXUDUCBQHIA-UHFFFAOYSA-N 5-chloro-3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-phenyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=C(Cl)N=C1C1=CC=CC=C1 ICJSXUDUCBQHIA-UHFFFAOYSA-N 0.000 description 2
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
• 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 238000007126 N-alkylation reaction Methods 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 238000006619 Stille reaction Methods 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• CJYXCQLOZNIMFP-UHFFFAOYSA-N azocan-2-one Chemical compound O=C1CCCCCCN1 CJYXCQLOZNIMFP-UHFFFAOYSA-N 0.000 description 2
• QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 150000001733 carboxylic acid esters Chemical class 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• 150000001879 copper Chemical class 0.000 description 2
• 101150111293 cor-1 gene Proteins 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 238000006880 cross-coupling reaction Methods 0.000 description 2
• GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000001033 ether group Chemical group 0.000 description 2
• ZZKVCSNQJQUHGF-UHFFFAOYSA-N ethyl 2-(4-chlorophenyl)-1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-4-carboxylate Chemical compound C=1C=C(Cl)C=CC=1C1=NC(C(=O)OCC)=CN1CC(=NO1)C=C1C1=CC=C(Cl)S1 ZZKVCSNQJQUHGF-UHFFFAOYSA-N 0.000 description 2
• OFFLCPCBXQALTD-UHFFFAOYSA-N ethyl 2-(4-chlorophenyl)-1h-imidazole-5-carboxylate Chemical compound N1C(C(=O)OCC)=CN=C1C1=CC=C(Cl)C=C1 OFFLCPCBXQALTD-UHFFFAOYSA-N 0.000 description 2
• AIUYNVLWDRHBTI-UHFFFAOYSA-N ethyl 2-cyano-5-methyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC(C#N)=NC=1C AIUYNVLWDRHBTI-UHFFFAOYSA-N 0.000 description 2
• CZERPLCWZBSYIZ-UHFFFAOYSA-N ethyl 2-ethylsulfonyl-1h-imidazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(S(=O)(=O)CC)N1 CZERPLCWZBSYIZ-UHFFFAOYSA-N 0.000 description 2
• CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 description 2
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 125000005956 isoquinolyl group Chemical group 0.000 description 2
• 239000004310 lactic acid Substances 0.000 description 2
• 235000014655 lactic acid Nutrition 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• GEPGABWGJBHEOW-UHFFFAOYSA-N methyl 2-[2-(2-methoxyethoxy)ethoxymethyl]-1h-imidazole-5-carboxylate Chemical compound COCCOCCOCC1=NC=C(C(=O)OC)N1 GEPGABWGJBHEOW-UHFFFAOYSA-N 0.000 description 2
• LXQRPAYQDDYRDZ-UHFFFAOYSA-N methyl 3-[(1-amino-2-methoxyethylidene)amino]oxyprop-2-enoate Chemical compound COCC(=N)NOC=CC(=O)OC LXQRPAYQDDYRDZ-UHFFFAOYSA-N 0.000 description 2
• XHJMXMOVEKMCAA-UHFFFAOYSA-N methyl 3-[1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazol-4-yl]propanoate Chemical compound C1=NC(CCC(=O)OC)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 XHJMXMOVEKMCAA-UHFFFAOYSA-N 0.000 description 2
• GDNPYEAMKCNBCW-UHFFFAOYSA-N methyl 3-[[1-amino-2-[2-(2-methoxyethoxy)ethoxy]ethylidene]amino]oxyprop-2-enoate Chemical compound COCCOCCOCC(=N)NOC=CC(=O)OC GDNPYEAMKCNBCW-UHFFFAOYSA-N 0.000 description 2
• AIQIRMAMHUGRBL-UHFFFAOYSA-N methyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(methoxymethyl)imidazole-4-carboxylate Chemical compound COCC1=NC=C(C(=O)OC)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 AIQIRMAMHUGRBL-UHFFFAOYSA-N 0.000 description 2
• MKHJQMJKKJFMJB-UHFFFAOYSA-N methyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-4-carboxylate Chemical compound COC(=O)C1=CN=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 MKHJQMJKKJFMJB-UHFFFAOYSA-N 0.000 description 2
• VHEGNNVBVKMOOC-UHFFFAOYSA-N methyl 5-chloro-2-phenyl-1h-imidazole-4-carboxylate Chemical compound ClC1=C(C(=O)OC)NC(C=2C=CC=CC=2)=N1 VHEGNNVBVKMOOC-UHFFFAOYSA-N 0.000 description 2
• RKLLZTAGGTZGHC-UHFFFAOYSA-N methyl 5-methyl-2-phenyl-1h-imidazole-4-carboxylate Chemical compound CC1=C(C(=O)OC)NC(C=2C=CC=CC=2)=N1 RKLLZTAGGTZGHC-UHFFFAOYSA-N 0.000 description 2
• IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 2
• 239000003094 microcapsule Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• UNKQCVYVFHGUTQ-UHFFFAOYSA-N n'-hydroxy-2-methoxyethanimidamide Chemical compound COCC(N)=NO UNKQCVYVFHGUTQ-UHFFFAOYSA-N 0.000 description 2
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• 229910052759 nickel Inorganic materials 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• BTLSLHNLDQCWKS-UHFFFAOYSA-N oxocan-2-one Chemical compound O=C1CCCCCCO1 BTLSLHNLDQCWKS-UHFFFAOYSA-N 0.000 description 2
• HZIVRQOIUMAXID-UHFFFAOYSA-N oxocane Chemical compound C1CCCOCCC1 HZIVRQOIUMAXID-UHFFFAOYSA-N 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 230000001376 precipitating effect Effects 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 108010014806 prothrombinase complex Proteins 0.000 description 2
• 125000005494 pyridonyl group Chemical group 0.000 description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000003001 serine protease inhibitor Substances 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 238000005694 sulfonylation reaction Methods 0.000 description 2
• 150000003462 sulfoxides Chemical class 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• BOCWGBMVJKSUOD-UHFFFAOYSA-N tert-butyl 1h-imidazole-5-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=CN1 BOCWGBMVJKSUOD-UHFFFAOYSA-N 0.000 description 2
• WINGEFIITRDOLJ-UHFFFAOYSA-N tert-butyl 2-hydroxyacetate Chemical compound CC(C)(C)OC(=O)CO WINGEFIITRDOLJ-UHFFFAOYSA-N 0.000 description 2
• SYXBLASQKPONBN-UHFFFAOYSA-N tert-butyl n-(1-propan-2-ylpiperidin-4-yl)carbamate Chemical compound CC(C)N1CCC(NC(=O)OC(C)(C)C)CC1 SYXBLASQKPONBN-UHFFFAOYSA-N 0.000 description 2
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
• XHTORJWGZKCDGL-GRGSLBFTSA-N (2s)-1-[(2r,3r)-2-amino-3-methylpentanoyl]-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide Chemical compound CC[C@@H](C)[C@@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 XHTORJWGZKCDGL-GRGSLBFTSA-N 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
• TXLLFXVNIJXUQJ-UHFFFAOYSA-N 1,3-oxazocan-2-one Chemical compound O=C1NCCCCCO1 TXLLFXVNIJXUQJ-UHFFFAOYSA-N 0.000 description 1
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
• NZBVQPIZDGSDNN-UHFFFAOYSA-N 1,4-oxazocane Chemical compound C1CCOCCNC1 NZBVQPIZDGSDNN-UHFFFAOYSA-N 0.000 description 1
• WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
• OHUMKYGINIODOY-UHFFFAOYSA-N 1-(1-methylpiperidin-4-yl)piperazine Chemical compound C1CN(C)CCC1N1CCNCC1 OHUMKYGINIODOY-UHFFFAOYSA-N 0.000 description 1
• LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 1
• SCBZBMXPJYMXRC-UHFFFAOYSA-N 1-(bromomethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CBr)=C1 SCBZBMXPJYMXRC-UHFFFAOYSA-N 0.000 description 1
• ZFTCZZRSBKPVRI-UHFFFAOYSA-N 1-[(3,4-difluorophenyl)methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=CN1CC1=CC=C(F)C(F)=C1 ZFTCZZRSBKPVRI-UHFFFAOYSA-N 0.000 description 1
• ADMPQBOXAFPXSM-UHFFFAOYSA-N 1-[(3,4-difluorophenyl)methyl]-n-[(1-propan-2-ylpiperidin-4-yl)methyl]imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1CNC(=O)C1=NC=CN1CC1=CC=C(F)C(F)=C1 ADMPQBOXAFPXSM-UHFFFAOYSA-N 0.000 description 1
• DSRWWZSKXZGVBH-UHFFFAOYSA-N 1-[(3-chlorophenyl)methyl]-n-[(1-propan-2-ylpiperidin-4-yl)methyl]imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1CNC(=O)C1=NC=CN1CC1=CC=CC(Cl)=C1 DSRWWZSKXZGVBH-UHFFFAOYSA-N 0.000 description 1
• CPZFDIMLMSZWGK-UHFFFAOYSA-N 1-[(3-chlorophenyl)methyl]imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1CC1=CC=CC(Cl)=C1 CPZFDIMLMSZWGK-UHFFFAOYSA-N 0.000 description 1
• ZDDWJNLKFSYDPU-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=CN1CC1=CC=CC(F)=C1 ZDDWJNLKFSYDPU-UHFFFAOYSA-N 0.000 description 1
• YDFLJIZYQDPAOX-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(=O)NC2CCN(CC2)C(C)C)=C1 YDFLJIZYQDPAOX-UHFFFAOYSA-N 0.000 description 1
• KUAVZOIRPFSSEN-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-n-[(1-pyridin-4-ylazetidin-3-yl)methyl]imidazole-2-carboxamide Chemical compound COC1=CC=CC(CN2C(=NC=C2)C(=O)NCC2CN(C2)C=2C=CN=CC=2)=C1 KUAVZOIRPFSSEN-UHFFFAOYSA-N 0.000 description 1
• DICXAMCEVUXDQO-UHFFFAOYSA-N 1-[2-(4-chloroanilino)-2-oxoethyl]-2-(methoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound COCC1=NC(C(=O)NC2CCN(CC2)C(C)C)=CN1CC(=O)NC1=CC=C(Cl)C=C1 DICXAMCEVUXDQO-UHFFFAOYSA-N 0.000 description 1
• SAXBWNKXLRTUCE-UHFFFAOYSA-N 1-[2-(4-chloroanilino)-2-oxoethyl]-2-(methoxymethyl)imidazole-4-carboxylic acid Chemical compound COCC1=NC(C(O)=O)=CN1CC(=O)NC1=CC=C(Cl)C=C1 SAXBWNKXLRTUCE-UHFFFAOYSA-N 0.000 description 1
• YYPQZZZONOMMPE-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=CN1CCC1=CC=C(Cl)C=C1 YYPQZZZONOMMPE-UHFFFAOYSA-N 0.000 description 1
• QGPOFNSECITISC-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(methoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound COCC1=NC(C(=O)NC2CCN(CC2)C(C)C)=CN1CC(=NO1)C=C1C1=CC=C(Cl)S1 QGPOFNSECITISC-UHFFFAOYSA-N 0.000 description 1
• MGAHEZZMWGSUIJ-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(methoxymethyl)-n-[4-(2-methylsulfonylphenyl)phenyl]imidazole-4-carboxamide Chemical compound COCC1=NC(C(=O)NC=2C=CC(=CC=2)C=2C(=CC=CC=2)S(C)(=O)=O)=CN1CC(=NO1)C=C1C1=CC=C(Cl)S1 MGAHEZZMWGSUIJ-UHFFFAOYSA-N 0.000 description 1
• ZINPKRUSKZJSHD-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-iodo-5-methylimidazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)N=C(I)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 ZINPKRUSKZJSHD-UHFFFAOYSA-N 0.000 description 1
• AMKFNKDQAXOADF-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-4-(3-hydroxyazetidine-1-carbonyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C(=O)N2CC(O)C2)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 AMKFNKDQAXOADF-UHFFFAOYSA-N 0.000 description 1
• NNNSXFHGYWUQAW-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-4-(3-methoxyazetidine-1-carbonyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-2-carboxamide Chemical compound C1C(OC)CN1C(=O)C(N=C1C(=O)NC2CCN(CC2)C(C)C)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 NNNSXFHGYWUQAW-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• OIWIYLWZIIJNHU-UHFFFAOYSA-N 1-sulfanylpyrazole Chemical compound SN1C=CC=N1 OIWIYLWZIIJNHU-UHFFFAOYSA-N 0.000 description 1
• XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
• YOYAIZYFCNQIRF-UHFFFAOYSA-N 2,6-dichlorobenzonitrile Chemical compound ClC1=CC=CC(Cl)=C1C#N YOYAIZYFCNQIRF-UHFFFAOYSA-N 0.000 description 1
• BNBRIFIJRKJGEI-UHFFFAOYSA-N 2,6-difluorobenzonitrile Chemical compound FC1=CC=CC(F)=C1C#N BNBRIFIJRKJGEI-UHFFFAOYSA-N 0.000 description 1
• LXJMSJXMDSEKFZ-UHFFFAOYSA-N 2-(2-methoxyethoxymethyl)-n-(1-propan-2-ylpiperidin-4-yl)-1h-imidazole-5-carboxamide Chemical compound N1C(COCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 LXJMSJXMDSEKFZ-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• TXNHACCENVFVHL-UHFFFAOYSA-N 2-[2-(2-methoxyethoxy)ethoxymethyl]-1H-imidazole-5-carboxylic acid methyl 2-[2-(2-methoxyethoxy)ethoxymethyl]-1H-imidazole-5-carboxylate Chemical compound COCCOCCOCc1ncc([nH]1)C(O)=O.COCCOCCOCc1ncc([nH]1)C(=O)OC TXNHACCENVFVHL-UHFFFAOYSA-N 0.000 description 1
• XFQZJPUBFKJWIH-UHFFFAOYSA-N 2-[2-(2-methoxyethoxy)ethoxymethyl]-1h-imidazole-5-carboxylic acid Chemical compound COCCOCCOCC1=NC=C(C(O)=O)N1 XFQZJPUBFKJWIH-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• YSTUPBOIUOUMHG-UHFFFAOYSA-N 2-bromo-n-(4-chlorophenyl)acetamide Chemical compound ClC1=CC=C(NC(=O)CBr)C=C1 YSTUPBOIUOUMHG-UHFFFAOYSA-N 0.000 description 1
• REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
• LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• VPTJWIQPFBOONE-UHFFFAOYSA-N 2-carbamoyl-3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methylimidazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)N=C(C(N)=O)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 VPTJWIQPFBOONE-UHFFFAOYSA-N 0.000 description 1
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
• MWOOOBMFLYUDTN-UHFFFAOYSA-N 2-ethylsulfanyliminoacetic acid Chemical compound CCSN=CC(O)=O MWOOOBMFLYUDTN-UHFFFAOYSA-N 0.000 description 1
• YYRJTQRYMNMUCR-UHFFFAOYSA-N 2-methyl-1,3-thiazole-4-carbonitrile Chemical compound CC1=NC(C#N)=CS1 YYRJTQRYMNMUCR-UHFFFAOYSA-N 0.000 description 1
• 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• HEPPAPZASXFWTB-UHFFFAOYSA-N 3,3-dibromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)C(Br)Br HEPPAPZASXFWTB-UHFFFAOYSA-N 0.000 description 1
• OGOBINRVCUWLGN-UHFFFAOYSA-N 3-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=CC(C#N)=C1 OGOBINRVCUWLGN-UHFFFAOYSA-N 0.000 description 1
• RJIUHSPTTDOIHE-UHFFFAOYSA-N 3-[2-(4-chlorophenyl)ethyl]-2-[2-(2-methoxyethoxy)ethoxymethyl]-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1CCN1C(COCCOCCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 RJIUHSPTTDOIHE-UHFFFAOYSA-N 0.000 description 1
• IABNUPVNSSGKRB-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(2-methoxyethyl)-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(CCOC)=NC=C1C(=O)NC1CCN(C(C)C)CC1 IABNUPVNSSGKRB-UHFFFAOYSA-N 0.000 description 1
• BDBIZVAXKJPFFD-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-(methoxymethyl)imidazole-4-carboxylic acid Chemical compound COCC1=NC=C(C(O)=O)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 BDBIZVAXKJPFFD-UHFFFAOYSA-N 0.000 description 1
• OITGXSFSLFFZOA-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-cyclopentyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1CCCC1 OITGXSFSLFFZOA-UHFFFAOYSA-N 0.000 description 1
• GNXBQDFYLGUOBA-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-cyclopropyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1CC1 GNXBQDFYLGUOBA-UHFFFAOYSA-N 0.000 description 1
• CLIZAIKFZPTUBG-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-iodo-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N=C(I)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 CLIZAIKFZPTUBG-UHFFFAOYSA-N 0.000 description 1
• MDOQAYPINULBNR-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-propan-2-yl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=CN=C(C(C)C)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 MDOQAYPINULBNR-UHFFFAOYSA-N 0.000 description 1
• XGFZOQWHELPOEC-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-pyridin-2-ylimidazole-4-carboxylic acid Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(C(=O)O)=CN=C1C1=CC=CC=N1 XGFZOQWHELPOEC-UHFFFAOYSA-N 0.000 description 1
• PIALTOHZCCLNHB-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-2-phenylimidazole-4-carboxylic acid Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(C(O)=O)=C(C)N=C1C1=CC=CC=C1 PIALTOHZCCLNHB-UHFFFAOYSA-N 0.000 description 1
• YDXWWFFMYIVTTB-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=C(C)N=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 YDXWWFFMYIVTTB-UHFFFAOYSA-N 0.000 description 1
• LHKZCUIWDDEBFL-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-2-pyridin-2-ylimidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC2=NOC(=C2)C=2SC(Cl)=CC=2)=CN=C1C1=CC=CC=N1 LHKZCUIWDDEBFL-UHFFFAOYSA-N 0.000 description 1
• AXWDVKWOAFVUGH-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-2,4-dicarboxylic acid Chemical compound OC(=O)C1=CN=C(C(O)=O)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 AXWDVKWOAFVUGH-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
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• KSXGQRBTBLQJEF-UHFFFAOYSA-N 3-methoxyazetidine;hydrochloride Chemical compound Cl.COC1CNC1 KSXGQRBTBLQJEF-UHFFFAOYSA-N 0.000 description 1
• OOWFYDWAMOKVSF-UHFFFAOYSA-N 3-methoxypropanenitrile Chemical compound COCCC#N OOWFYDWAMOKVSF-UHFFFAOYSA-N 0.000 description 1
• CUMCMYMKECWGHO-UHFFFAOYSA-N 3-methyl-1,2-oxazole Chemical compound CC=1C=CON=1 CUMCMYMKECWGHO-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• JJIFTOPVKWDHJI-UHFFFAOYSA-N 4-(bromomethyl)-1,2-difluorobenzene Chemical compound FC1=CC=C(CBr)C=C1F JJIFTOPVKWDHJI-UHFFFAOYSA-N 0.000 description 1
• QBGONPQFBDUVPG-UHFFFAOYSA-N 4-chloro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=CC=C(Cl)C=C1 QBGONPQFBDUVPG-UHFFFAOYSA-N 0.000 description 1
• HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
• AHJRNCWETDBFRL-UHFFFAOYSA-N 4-o-tert-butyl 2-o-ethyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]imidazole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=NC(C(=O)OC(C)(C)C)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 AHJRNCWETDBFRL-UHFFFAOYSA-N 0.000 description 1
• CXPDHIAQLUQKBB-UHFFFAOYSA-N 5-chloro-3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-phenyl-n-(1-propan-2-ylpiperidin-4-yl)imidazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C(N1CC(=O)NC=2N=CC(Cl)=CC=2)=C(Cl)N=C1C1=CC=CC=C1 CXPDHIAQLUQKBB-UHFFFAOYSA-N 0.000 description 1
• MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• ULHLTDXPKWELHQ-UHFFFAOYSA-N 5-methyl-imidazole-4-carboxylic acid Chemical compound CC=1NC=NC=1C(O)=O ULHLTDXPKWELHQ-UHFFFAOYSA-N 0.000 description 1
• BHKTWIPEAFACTC-UHFFFAOYSA-N 5-o-tert-butyl 2-o-ethyl 1h-imidazole-2,5-dicarboxylate Chemical compound CCOC(=O)C1=NC=C(C(=O)OC(C)(C)C)N1 BHKTWIPEAFACTC-UHFFFAOYSA-N 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 206010003162 Arterial injury Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 238000006418 Brown reaction Methods 0.000 description 1
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 description 1
• NQYPSLDSUZWOJY-UHFFFAOYSA-N CC(C)(C)OC(=O)C1=CN=C(N1)C(=O)N2CCCOCC2 Chemical compound CC(C)(C)OC(=O)C1=CN=C(N1)C(=O)N2CCCOCC2 NQYPSLDSUZWOJY-UHFFFAOYSA-N 0.000 description 1
• FYLCPKFKLPYZDG-UHFFFAOYSA-N COCC1=NC=CN1CC2=NOC(=C2)C3=CC=C(S3)Cl Chemical compound COCC1=NC=CN1CC2=NOC(=C2)C3=CC=C(S3)Cl FYLCPKFKLPYZDG-UHFFFAOYSA-N 0.000 description 1
• 229910014813 CaC2 Inorganic materials 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• YFDZEBHOWUXYNI-UHFFFAOYSA-N ClC1=CC=C(S1)C1=CC(=NO1)CN1C(=NC=C1)C(=O)O.C(C)(C)N1CCC(CC1)NC(=O)C=1N(C=CN1)CCC1=CC=C(C=C1)Cl Chemical compound ClC1=CC=C(S1)C1=CC(=NO1)CN1C(=NC=C1)C(=O)O.C(C)(C)N1CCC(CC1)NC(=O)C=1N(C=CN1)CCC1=CC=C(C=C1)Cl YFDZEBHOWUXYNI-UHFFFAOYSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• 108010088842 Fibrinolysin Proteins 0.000 description 1
• 101100134922 Gallus gallus COR5 gene Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• VSFNAZLYGOOSEY-UHFFFAOYSA-N Imidazolylpropionic acid Natural products OC(=O)CCN1C=CN=C1 VSFNAZLYGOOSEY-UHFFFAOYSA-N 0.000 description 1
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
• NQTWTFRKFPLPIX-UHFFFAOYSA-N N-(azetidin-3-yl)pyridin-4-amine Chemical compound C1NCC1NC1=CC=NC=C1 NQTWTFRKFPLPIX-UHFFFAOYSA-N 0.000 description 1
• 230000006181 N-acylation Effects 0.000 description 1
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical group O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
• 241000282520 Papio Species 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 108010022999 Serine Proteases Proteins 0.000 description 1
• 102000012479 Serine Proteases Human genes 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 229940122388 Thrombin inhibitor Drugs 0.000 description 1
• 208000032109 Transient ischaemic attack Diseases 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• RWLXRSVKLGCJGK-UHFFFAOYSA-N [2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl] 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]imidazole-4-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C(=O)OCC(=O)OC(C)(C)C)=CN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 RWLXRSVKLGCJGK-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 238000007171 acid catalysis Methods 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 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
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 230000002785 anti-thrombosis Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 150000001499 aryl bromides Chemical class 0.000 description 1
• 150000001501 aryl fluorides Chemical class 0.000 description 1
• 150000005840 aryl radicals Chemical class 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 150000004651 carbonic acid esters Chemical class 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• JUQJCAMVXDQFCM-UHFFFAOYSA-N chembl561056 Chemical compound O1N=C(C)C=C1C1=C(C=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)NN=C1 JUQJCAMVXDQFCM-UHFFFAOYSA-N 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
• 239000003593 chromogenic compound Substances 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 230000035602 clotting Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
• 239000004914 cyclooctane Substances 0.000 description 1
• URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 description 1
• 239000004913 cyclooctene Substances 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• SVPZJHKVRMRREG-UHFFFAOYSA-N cyclopentanecarbonitrile Chemical compound N#CC1CCCC1 SVPZJHKVRMRREG-UHFFFAOYSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 1
• KXPZAGCPFFFOLO-UHFFFAOYSA-N cyclopropylmethyl 1H-imidazole-5-carboxylate Chemical compound C1(CC1)COC(=O)C=1N=CNC=1 KXPZAGCPFFFOLO-UHFFFAOYSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical compound C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
• 239000012954 diazonium Substances 0.000 description 1
• 150000001989 diazonium salts Chemical class 0.000 description 1
• ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical compound OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 description 1
• RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• UHYNYIGCGVDBTC-UHFFFAOYSA-N ethyl 1h-imidazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=CN1 UHYNYIGCGVDBTC-UHFFFAOYSA-N 0.000 description 1
• TYQKOXJDUSYFTD-UHFFFAOYSA-N ethyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-iodo-5-methylimidazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(I)N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 TYQKOXJDUSYFTD-UHFFFAOYSA-N 0.000 description 1
• VLDUBDZWWNLZCU-UHFFFAOYSA-N ethyl 5-methyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC=NC=1C VLDUBDZWWNLZCU-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000003682 fluorination reaction Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• HNTXFQLKQWBPLG-UHFFFAOYSA-M hexadecyl(trimethyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](C)(C)C HNTXFQLKQWBPLG-UHFFFAOYSA-M 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
• JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
• JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 239000003978 infusion fluid Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
• 108010075079 isoleucyl-prolyl-arginine-4-nitroanilide Proteins 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 238000003367 kinetic assay Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 125000005905 mesyloxy group Chemical group 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 238000006263 metalation reaction Methods 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• GANOFONOHGNMDB-UHFFFAOYSA-N methyl 2-ethyl-5-methyl-1h-imidazole-4-carboxylate Chemical compound CCC1=NC(C)=C(C(=O)OC)N1 GANOFONOHGNMDB-UHFFFAOYSA-N 0.000 description 1
• ATDOXHMHMKWMJG-UHFFFAOYSA-N methyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-methyl-2-phenylimidazole-4-carboxylate Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C(C(=O)OC)=C(C)N=C1C1=CC=CC=C1 ATDOXHMHMKWMJG-UHFFFAOYSA-N 0.000 description 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• ZSBGJIPLRFDOJE-UHFFFAOYSA-N n-(4-phenylphenyl)methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=CC=CC=C1 ZSBGJIPLRFDOJE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• AQNQGBUEVCAVML-UHFFFAOYSA-N oxazepane Chemical compound C1CCNOCC1 AQNQGBUEVCAVML-UHFFFAOYSA-N 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• JLPGSSHHLKZYMJ-UHFFFAOYSA-N piperidin-4-amine;hydrochloride Chemical compound Cl.NC1CCNCC1 JLPGSSHHLKZYMJ-UHFFFAOYSA-N 0.000 description 1
• 229940012957 plasmin Drugs 0.000 description 1
• 229920005990 polystyrene resin Polymers 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• IWRRRCZSVINKHU-UHFFFAOYSA-N pyrazol-3-ylidenemethanone Chemical class O=C=C1C=CN=N1 IWRRRCZSVINKHU-UHFFFAOYSA-N 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
• 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
• 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
• 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 235000017550 sodium carbonate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 229910000080 stannane Inorganic materials 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 230000006103 sulfonylation Effects 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 238000006557 surface reaction Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
• CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 239000003868 thrombin inhibitor Substances 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
• 238000005809 transesterification reaction Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 201000010875 transient cerebral ischemia Diseases 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• 239000005051 trimethylchlorosilane Substances 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 229960001322 trypsin Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 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
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1