AU2004238498B2 - Triazole-derivatives as factor Xa inhibitors - Google Patents

Info

Publication number

AU2004238498B2

AU2004238498B2 AU2004238498A AU2004238498A AU2004238498B2 AU 2004238498 B2 AU2004238498 B2 AU 2004238498B2 AU 2004238498 A AU2004238498 A AU 2004238498A AU 2004238498 A AU2004238498 A AU 2004238498A AU 2004238498 B2 AU2004238498 B2 AU 2004238498B2

Authority

AU

Australia

Prior art keywords

alkyl

another

unsubstituted

alkylene

mono

Prior art date

2003-05-19

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

• 229940123583 Factor Xa inhibitor Drugs 0.000 title description 2
• 229940042055 systemic antimycotics triazole derivative Drugs 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 147
• ZRQQXFMGYSOKDF-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine Chemical compound CC(C)N1CCC(N)CC1 ZRQQXFMGYSOKDF-UHFFFAOYSA-N 0.000 claims description 8
• KGFWAMSYIURHEM-UHFFFAOYSA-N 2-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)tetrazole-5-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NN(CC2=NOC(=C2)C=2SC(Cl)=CC=2)N=N1 KGFWAMSYIURHEM-UHFFFAOYSA-N 0.000 claims description 3
• BDTOTMBOHYUNSQ-UHFFFAOYSA-N triazole-1-carboxylic acid Chemical compound OC(=O)N1C=CN=N1 BDTOTMBOHYUNSQ-UHFFFAOYSA-N 0.000 claims description 3
• MUXSXTKRNCHFTL-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-phenyl-n-(1-propan-2-ylpiperidin-4-yl)-1,2,4-triazole-3-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NN(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(C=2C=CC=CC=2)=N1 MUXSXTKRNCHFTL-UHFFFAOYSA-N 0.000 claims 1
• 108010074860 Factor Xa Proteins 0.000 abstract description 39
• 238000000034 method Methods 0.000 abstract description 35
• 230000005764 inhibitory process Effects 0.000 abstract description 22
• 230000000694 effects Effects 0.000 abstract description 20
• 239000000825 pharmaceutical preparation Substances 0.000 abstract description 12
• 238000011321 prophylaxis Methods 0.000 abstract description 12
• 238000002560 therapeutic procedure Methods 0.000 abstract description 12
• 239000003814 drug Substances 0.000 abstract description 11
• 230000023555 blood coagulation Effects 0.000 abstract description 10
• 239000003112 inhibitor Substances 0.000 abstract description 10
• 238000002360 preparation method Methods 0.000 abstract description 10
• 239000004480 active ingredient Substances 0.000 abstract description 6
• 230000008569 process Effects 0.000 abstract description 6
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 5
• 208000001435 Thromboembolism Diseases 0.000 abstract description 5
• 230000002265 prevention Effects 0.000 abstract description 4
• 230000002441 reversible effect Effects 0.000 abstract description 4
• 230000002785 anti-thrombosis Effects 0.000 abstract description 2
• 108010054265 Factor VIIa Proteins 0.000 abstract 4
• 229940012414 factor viia Drugs 0.000 abstract 4
• -1 phenylpyridyl Chemical group 0.000 description 210
• 125000000623 heterocyclic group Chemical group 0.000 description 97
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 69
• 125000000217 alkyl group Chemical group 0.000 description 64
• 125000003118 aryl group Chemical group 0.000 description 56
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 55
• 150000003536 tetrazoles Chemical class 0.000 description 52
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 51
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 50
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 50
• 229910052736 halogen Inorganic materials 0.000 description 47
• 150000002367 halogens Chemical class 0.000 description 47
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 47
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 45
• 229910052799 carbon Inorganic materials 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 41
• 125000004122 cyclic group Chemical group 0.000 description 41
• 150000003839 salts Chemical class 0.000 description 41
• 229910052757 nitrogen Inorganic materials 0.000 description 37
• 150000003852 triazoles Chemical class 0.000 description 37
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 36
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 35
• 125000002950 monocyclic group Chemical group 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 29
• 239000000651 prodrug Substances 0.000 description 29
• 229940002612 prodrug Drugs 0.000 description 29
• 125000002619 bicyclic group Chemical group 0.000 description 28
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 27
• 230000015572 biosynthetic process Effects 0.000 description 27
• 125000004093 cyano group Chemical group *C#N 0.000 description 27
• 239000000203 mixture Substances 0.000 description 26
• 238000003786 synthesis reaction Methods 0.000 description 25
• 125000004076 pyridyl group Chemical group 0.000 description 23
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 23
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 22
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 22
• 125000005842 heteroatom Chemical group 0.000 description 22
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 22
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 21
• 125000000753 cycloalkyl group Chemical group 0.000 description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 21
• 229910052760 oxygen Inorganic materials 0.000 description 21
• 229910052717 sulfur Inorganic materials 0.000 description 21
• 239000011593 sulfur Substances 0.000 description 21
• 125000001544 thienyl group Chemical group 0.000 description 21
• MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 description 20
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 20
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 20
• 239000000460 chlorine Substances 0.000 description 20
• 229910052739 hydrogen Inorganic materials 0.000 description 20
• 239000001301 oxygen Substances 0.000 description 20
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 19
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 19
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 18
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 18
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 18
• 239000001257 hydrogen Substances 0.000 description 18
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 description 18
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 18
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 17
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 17
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 17
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 17
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 17
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 17
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 17
• 229910052801 chlorine Inorganic materials 0.000 description 17
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 17
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 17
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 16
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
• 125000004429 atom Chemical group 0.000 description 16
• 229910052731 fluorine Inorganic materials 0.000 description 16
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 15
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 15
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 15
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 15
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 15
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• 238000003556 assay Methods 0.000 description 13
• PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 description 13
• 239000011737 fluorine Substances 0.000 description 13
• 125000001041 indolyl group Chemical group 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
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 12
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 12
• 125000004432 carbon atom Chemical group C* 0.000 description 12
• 125000000524 functional group Chemical group 0.000 description 12
• 125000002883 imidazolyl group Chemical group 0.000 description 12
• 125000000842 isoxazolyl group Chemical group 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
• 125000003373 pyrazinyl group Chemical group 0.000 description 12
• 125000003226 pyrazolyl group Chemical group 0.000 description 12
• 125000002098 pyridazinyl group Chemical group 0.000 description 12
• 125000000168 pyrrolyl group Chemical group 0.000 description 12
• 125000000335 thiazolyl group Chemical group 0.000 description 12
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-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
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 11
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 11
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 11
• 239000003153 chemical reaction reagent Substances 0.000 description 11
• 239000003795 chemical substances by application Substances 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
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 11
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 11
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 11
• 125000001786 isothiazolyl group Chemical group 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
• 125000000714 pyrimidinyl group Chemical group 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
• 239000000243 solution Substances 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
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 229910052794 bromium Inorganic materials 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 10
• 125000002541 furyl 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
• 125000002053 thietanyl group Chemical group 0.000 description 10
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 125000001153 fluoro group Chemical group F* 0.000 description 9
• 229910052740 iodine Inorganic materials 0.000 description 9
• 230000002829 reductive effect Effects 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
• 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
• XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• 239000003146 anticoagulant agent Substances 0.000 description 8
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
• 229940088598 enzyme Drugs 0.000 description 8
• 239000002243 precursor Substances 0.000 description 8
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 7
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 7
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
• 208000007536 Thrombosis Diseases 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 125000003971 isoxazolinyl group Chemical group 0.000 description 7
• 125000001624 naphthyl group Chemical group 0.000 description 7
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 239000000758 substrate Substances 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
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
• 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
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 6
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 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
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 6
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 6
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 6
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 6
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 6
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 6
• 150000001735 carboxylic acids Chemical class 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 6
• 125000002757 morpholinyl 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
• 125000003386 piperidinyl group Chemical group 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 6
• 238000010561 standard procedure Methods 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 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
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 5
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 5
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 5
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 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
• 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 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
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 5
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 5
• 125000002252 acyl group Chemical group 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
• 125000004623 carbolinyl group Chemical group 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 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
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 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
• 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
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 5
• 125000001715 oxadiazolyl group Chemical group 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
• 125000004193 piperazinyl group Chemical group 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
• 239000007787 solid Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 125000003718 tetrahydrofuranyl group Chemical group 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
• 125000001113 thiadiazolyl group Chemical group 0.000 description 5
• 125000001984 thiazolidinyl group Chemical group 0.000 description 5
• 125000002769 thiazolinyl group Chemical group 0.000 description 5
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 5
• 238000011282 treatment Methods 0.000 description 5
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 5
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 4
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 4
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 4
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 4
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 4
• 125000000164 1,3-thiazinyl group Chemical group S1C(N=CC=C1)* 0.000 description 4
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 4
• 125000005955 1H-indazolyl group Chemical group 0.000 description 4
• JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 4
• XIKZTCXYFVSBJT-UHFFFAOYSA-N 3-pyrrol-1-yl-1h-1,2,4-triazole-5-carboxylic acid Chemical compound N1C(C(=O)O)=NC(N2C=CC=C2)=N1 XIKZTCXYFVSBJT-UHFFFAOYSA-N 0.000 description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
• 230000001154 acute effect Effects 0.000 description 4
• 125000002015 acyclic group Chemical group 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 125000002947 alkylene group Chemical group 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 229940127219 anticoagulant drug Drugs 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
• 239000003130 blood coagulation factor inhibitor Substances 0.000 description 4
• 125000002843 carboxylic acid group Chemical group 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 230000015271 coagulation Effects 0.000 description 4
• 238000005345 coagulation Methods 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
• 238000010828 elution Methods 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• 230000020764 fibrinolysis Effects 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 4
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 4
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 4
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 4
• 229960004072 thrombin Drugs 0.000 description 4
• 125000001425 triazolyl group Chemical group 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• 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
• 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
• XBTSMICULXRDAG-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-5-pyrrol-1-yl-1,2,4-triazole-3-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NN(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(N2C=CC=C2)=N1 XBTSMICULXRDAG-UHFFFAOYSA-N 0.000 description 3
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 3
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 238000007126 N-alkylation reaction Methods 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 238000002399 angioplasty Methods 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 238000006254 arylation reaction Methods 0.000 description 3
• 208000034158 bleeding Diseases 0.000 description 3
• 230000000740 bleeding effect Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 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
• 239000007903 gelatin capsule Substances 0.000 description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 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
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 238000002953 preparative HPLC Methods 0.000 description 3
• 208000037803 restenosis Diseases 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 3
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
• 230000002537 thrombolytic effect Effects 0.000 description 3
• 229910052723 transition metal Inorganic materials 0.000 description 3
• 150000003624 transition metals Chemical class 0.000 description 3
• 230000002792 vascular Effects 0.000 description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
• 125000006565 (C4-C7) cyclic group Chemical group 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
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 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
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
• IELJBQPUDFGBEL-UHFFFAOYSA-N 2-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]tetrazole-5-carboxylic acid Chemical compound N1=C(C(=O)O)N=NN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 IELJBQPUDFGBEL-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
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 206010002388 Angina unstable Diseases 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 239000005977 Ethylene Substances 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
• 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
• 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
• 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
• 208000007814 Unstable Angina Diseases 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 206010000891 acute myocardial infarction Diseases 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 2
• MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 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
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• 150000001879 copper Chemical class 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
• 238000002425 crystallisation Methods 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
• 239000003937 drug carrier Substances 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
• 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 2
• 238000001914 filtration Methods 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000028709 inflammatory response Effects 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
• 201000004332 intermediate coronary syndrome Diseases 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
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-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
• 229910052759 nickel Inorganic materials 0.000 description 2
• 125000002560 nitrile group Chemical group 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
• 125000001147 pentyl group Chemical group C(CCCC)* 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
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 108010014806 prothrombinase complex Proteins 0.000 description 2
• 125000005494 pyridonyl group Chemical group 0.000 description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000003001 serine protease inhibitor Substances 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• 238000005694 sulfonylation reaction Methods 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
• 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
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 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
• 238000005809 transesterification reaction Methods 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
• 210000003462 vein Anatomy 0.000 description 2
• NGUABMKOSJANPJ-SYIFMXBLSA-N (2r)-2-hydroxy-3-[[4-[2-[4-(trifluoromethoxy)phenyl]-2-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]ethyl]benzoyl]amino]propanoic acid Chemical compound C1=CC(C(=O)NC[C@@H](O)C(O)=O)=CC=C1CC(C=1C=CC(OC(F)(F)F)=CC=1)C1=NC(C=2C=CC(=CC=2)C(F)(F)F)=CS1 NGUABMKOSJANPJ-SYIFMXBLSA-N 0.000 description 1
• 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
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• 125000006650 (C2-C4) alkynyl 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
• FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 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
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
• OUNFHIJXTPWAGL-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-5-phenyl-1,2,4-triazole-3-carboxylic acid Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1N=C(C(=O)O)N=C1C1=CC=CC=C1 OUNFHIJXTPWAGL-UHFFFAOYSA-N 0.000 description 1
• YHVLHKDYUITXNE-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-5-pyridin-2-yl-1,2,4-triazole-3-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NN(CC2=NOC(=C2)C=2SC(Cl)=CC=2)C(C=2N=CC=CC=2)=N1 YHVLHKDYUITXNE-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
• 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
• SKZUXKOWTWFPPH-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine;hydrochloride Chemical compound Cl.CC(C)N1CCC(N)CC1 SKZUXKOWTWFPPH-UHFFFAOYSA-N 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
• 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
• XNMYNYSCEJBRPZ-UHFFFAOYSA-N 2-[(3-butyl-1-isoquinolinyl)oxy]-N,N-dimethylethanamine Chemical compound C1=CC=C2C(OCCN(C)C)=NC(CCCC)=CC2=C1 XNMYNYSCEJBRPZ-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
• KUICBYXMOLTTPZ-UHFFFAOYSA-N 2-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)-5-pyridin-2-yl-1,2,4-triazole-3-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC(C=2N=CC=CC=2)=NN1CC1=NOC(C=2SC(Cl)=CC=2)=C1 KUICBYXMOLTTPZ-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
• 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
• 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 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
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• GFGNJPGMLRGJBI-UHFFFAOYSA-N 3-phenyl-1h-1,2,4-triazole-5-carboxylic acid Chemical compound N1C(C(=O)O)=NC(C=2C=CC=CC=2)=N1 GFGNJPGMLRGJBI-UHFFFAOYSA-N 0.000 description 1
• KBNYLDUVTQSDNS-UHFFFAOYSA-N 3-pyridin-2-yl-1h-1,2,4-triazole-5-carboxylic acid Chemical compound OC(=O)C1=NNC(C=2N=CC=CC=2)=N1 KBNYLDUVTQSDNS-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
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-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
• 206010002383 Angina Pectoris 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
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 description 1
• 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 206010053567 Coagulopathies Diseases 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
• 208000005189 Embolism Diseases 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 108010088842 Fibrinolysin 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
• 239000007821 HATU Substances 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 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
• 238000005684 Liebig rearrangement reaction Methods 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
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 208000034486 Multi-organ failure Diseases 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 241000282520 Papio Species 0.000 description 1
• 208000010378 Pulmonary Embolism Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 108010022999 Serine Proteases Proteins 0.000 description 1
• 102000012479 Serine Proteases Human genes 0.000 description 1
• 229910008338 Si—(CH3) Inorganic materials 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 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
• 241000347391 Umbrina cirrosa Species 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 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 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• 238000007171 acid catalysis Methods 0.000 description 1
• 230000004913 activation Effects 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
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000004453 alkoxycarbonyl 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
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• 229940127090 anticoagulant agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 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
• 125000003725 azepanyl group Chemical group 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
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-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
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• 244000309464 bull Species 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
• 239000006227 byproduct Substances 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 125000002837 carbocyclic group Chemical group 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
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 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
• 238000007385 chemical modification Methods 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
• 239000011248 coating agent Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 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
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 239000012043 crude product Substances 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
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
• 238000013461 design Methods 0.000 description 1
• 239000012954 diazonium Substances 0.000 description 1
• 150000001989 diazonium salts Chemical class 0.000 description 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-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
• 208000035475 disorder Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution 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
• WDUYZCSZENDSPG-UHFFFAOYSA-N ethyl 2h-tetrazole-5-carboxylate;sodium Chemical compound [Na].CCOC(=O)C1=NN=NN1 WDUYZCSZENDSPG-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 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
• 238000003818 flash chromatography Methods 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
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 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
• 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
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
• 208000015181 infectious disease Diseases 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
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000003367 kinetic assay Methods 0.000 description 1
• 210000003127 knee Anatomy 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
• 210000004185 liver Anatomy 0.000 description 1
• 210000003141 lower extremity 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
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• FLHVRXNKCBFZJN-UHFFFAOYSA-N n-(1-propan-2-ylpiperidin-4-yl)-3-pyrrol-1-yl-1h-1,2,4-triazole-5-carboxamide Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NNC(N2C=CC=C2)=N1 FLHVRXNKCBFZJN-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 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
• 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000003835 nucleoside group Chemical group 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
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000012044 organic layer Substances 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
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000001575 pathological effect 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
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 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
• 125000004928 piperidonyl group Chemical group 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
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 239000002244 precipitate Substances 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
• 150000003141 primary amines Chemical class 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
• 238000000746 purification Methods 0.000 description 1
• IWRRRCZSVINKHU-UHFFFAOYSA-N pyrazol-3-ylidenemethanone Chemical class O=C=C1C=CN=N1 IWRRRCZSVINKHU-UHFFFAOYSA-N 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
• 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
• 230000036303 septic shock Effects 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000007921 spray 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
• 238000003756 stirring Methods 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
• 239000013589 supplement Substances 0.000 description 1
• 238000006557 surface reaction Methods 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000009885 systemic effect Effects 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
• 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
• ZVQXQPNJHRNGID-UHFFFAOYSA-N tetramethylsuccinonitrile Chemical compound N#CC(C)(C)C(C)(C)C#N ZVQXQPNJHRNGID-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 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
• 230000009424 thromboembolic effect Effects 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
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 201000010875 transient cerebral ischemia Diseases 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000008648 triflates Chemical class 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
• 230000009385 viral infection Effects 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