NO971415L - Aminoheterocykliske derivater som anti-trombose- eller antikoagulantmidler - Google Patents

Aminoheterocykliske derivater som anti-trombose- eller antikoagulantmidler

Info

Publication number: NO971415L
Authority: NO; Norway
Prior art keywords: group; alkyl; formula; ylcarbonyl; pyridyl
Prior art date: 1994-09-26

Application number

NO971415A

Other languages

English (en)

Norwegian (no)

Other versions

NO971415D0 (no

Inventor

Alan Wellington Faull

Colette Marie Mayo

John Preston

Andrew Stocker

Original Assignee

Zeneca Ltd

Priority date (The priority date 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 date listed.)

1994-09-26

Filing date

1997-03-25

Publication date

1997-05-22

1994-09-26 Priority claimed from GB9419341A external-priority patent/GB9419341D0/en

1994-12-21 Priority claimed from GBGB9425789.6A external-priority patent/GB9425789D0/en

1995-06-01 Priority claimed from GBGB9511051.6A external-priority patent/GB9511051D0/en

1997-03-25 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1997-03-25 Publication of NO971415D0 publication Critical patent/NO971415D0/no

1997-05-22 Publication of NO971415L publication Critical patent/NO971415L/no

Links

230000002785 anti-thrombosis Effects 0.000 title claims abstract description 9
239000003146 anticoagulant agent Substances 0.000 title abstract description 9
229940127090 anticoagulant agent Drugs 0.000 title abstract 2
229960004676 antithrombotic agent Drugs 0.000 title abstract 2
125000000217 alkyl group Chemical group 0.000 claims abstract description 271
238000000034 method Methods 0.000 claims abstract description 122
239000001257 hydrogen Substances 0.000 claims abstract description 107
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 107
125000002947 alkylene group Chemical group 0.000 claims abstract description 50
150000003839 salts Chemical class 0.000 claims abstract description 50
238000002360 preparation method Methods 0.000 claims abstract description 31
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 20
125000001624 naphthyl group Chemical group 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
-1 Pyrrolidin-1-ylcarbonyl Chemical group 0.000 claims description 373
125000001424 substituent group Chemical group 0.000 claims description 126
239000007858 starting material Substances 0.000 claims description 102
150000001875 compounds Chemical class 0.000 claims description 98
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 94
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 88
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 86
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 81
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
150000002431 hydrogen Chemical class 0.000 claims description 46
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 44
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 43
125000003545 alkoxy group Chemical group 0.000 claims description 41
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 41
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 37
239000002253 acid Substances 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 35
229910052736 halogen Inorganic materials 0.000 claims description 35
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 33
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 32
125000001072 heteroaryl group Chemical group 0.000 claims description 29
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 28
239000005977 Ethylene Substances 0.000 claims description 28
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 claims description 28
239000000460 chlorine Chemical group 0.000 claims description 27
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 26
125000004093 cyano group Chemical group *C#N 0.000 claims description 23
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 22
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 21
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 21
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 21
229910052794 bromium Inorganic materials 0.000 claims description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
229910052801 chlorine Inorganic materials 0.000 claims description 21
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 18
239000011737 fluorine Substances 0.000 claims description 17
229910052731 fluorine Inorganic materials 0.000 claims description 17
125000001153 fluoro group Chemical group F* 0.000 claims description 17
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 17
125000003282 alkyl amino group Chemical group 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
125000005842 heteroatom Chemical group 0.000 claims description 14
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 13
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
125000006358 carbonyl ethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([*:1])=O 0.000 claims description 11
125000004043 oxo group Chemical group O=* 0.000 claims description 11
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
125000005504 styryl group Chemical group 0.000 claims description 10
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 9
125000005368 heteroarylthio group Chemical group 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 9
125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
239000005864 Sulphur Substances 0.000 claims description 7
125000005236 alkanoylamino group Chemical group 0.000 claims description 7
125000006356 alkylene carbonyl group Chemical group 0.000 claims description 7
230000002429 anti-coagulating effect Effects 0.000 claims description 7
238000006460 hydrolysis reaction Methods 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 claims description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
230000007062 hydrolysis Effects 0.000 claims description 6
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
MHYKAABLWTVAFV-UHFFFAOYSA-N 4-(6-chloronaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 MHYKAABLWTVAFV-UHFFFAOYSA-N 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
238000007796 conventional method Methods 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
238000006900 dealkylation reaction Methods 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
UNVFDMNGCOELFO-UHFFFAOYSA-N ethyl 4-naphthalen-2-ylsulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 UNVFDMNGCOELFO-UHFFFAOYSA-N 0.000 claims description 4
IADXHFCIENFQHM-UHFFFAOYSA-N methyl 4-(6-chloronaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound COC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 IADXHFCIENFQHM-UHFFFAOYSA-N 0.000 claims description 4
OTAMSRPVNUTFEK-UHFFFAOYSA-N (1-naphthalen-2-ylsulfonylpiperidin-4-yl)-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCC1C(=O)N(CC1)CCN1C1=CC=NC=C1 OTAMSRPVNUTFEK-UHFFFAOYSA-N 0.000 claims description 3
NRXIFUFTSFRKJO-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 NRXIFUFTSFRKJO-UHFFFAOYSA-N 0.000 claims description 3
CPLQMNBLEGHTSN-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-1-yl)-(1-pyrimidin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=N1 CPLQMNBLEGHTSN-UHFFFAOYSA-N 0.000 claims description 3
NMZIEXPMYWMQNT-UHFFFAOYSA-N [1-(2-aminopyrimidin-4-yl)piperidin-4-yl]-[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]methanone Chemical compound NC1=NC=CC(N2CCC(CC2)C(=O)N2CCN(CC2)S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)=N1 NMZIEXPMYWMQNT-UHFFFAOYSA-N 0.000 claims description 3
FDHAGUWXSMNXSV-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(1-pyridazin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NN=C1 FDHAGUWXSMNXSV-UHFFFAOYSA-N 0.000 claims description 3
CZRZSYDVGNBPFW-UHFFFAOYSA-N [4-naphthalen-2-ylsulfonyl-2-(piperidine-1-carbonyl)piperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CCCCN1C(=O)C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 CZRZSYDVGNBPFW-UHFFFAOYSA-N 0.000 claims description 3
150000003973 alkyl amines Chemical class 0.000 claims description 3
229910021529 ammonia Inorganic materials 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
230000020335 dealkylation Effects 0.000 claims description 3
BFLBIGCXYCWLGC-UHFFFAOYSA-N ethyl 2-(naphthalen-2-ylsulfonylamino)-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propanoate Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(C(=O)OCC)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 BFLBIGCXYCWLGC-UHFFFAOYSA-N 0.000 claims description 3
ZNYCFMVRQWLGOP-UHFFFAOYSA-N ethyl 4-(6-bromonaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Br)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 ZNYCFMVRQWLGOP-UHFFFAOYSA-N 0.000 claims description 3
LXPBBYDFFDJFRH-UHFFFAOYSA-N ethyl 4-(6-chloronaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 LXPBBYDFFDJFRH-UHFFFAOYSA-N 0.000 claims description 3
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
ZUWIBQZMZXPSNJ-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-phenylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CC=1C=CC=CC=1)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 ZUWIBQZMZXPSNJ-UHFFFAOYSA-N 0.000 claims description 3
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 3
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
BRNZWCWDGKKFJP-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-n-[1-oxo-1-piperidin-1-yl-3-[[2-(4-pyridin-4-ylpiperazin-1-yl)acetyl]amino]propan-2-yl]acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)CN(CC1)CCN1C1=CC=NC=C1 BRNZWCWDGKKFJP-UHFFFAOYSA-N 0.000 claims description 2
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims description 2
125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 2
GCIDVUHOZMNNSY-UHFFFAOYSA-N [4-(4-phenylphenyl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 GCIDVUHOZMNNSY-UHFFFAOYSA-N 0.000 claims description 2
KCGIKXSPMXWZIO-UHFFFAOYSA-N [4-(6-bromonaphthalen-2-yl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC2=CC(Br)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 KCGIKXSPMXWZIO-UHFFFAOYSA-N 0.000 claims description 2
QXELHDVRNCLCKP-GIJQJNRQSA-N [4-[(e)-2-(4-bromophenyl)ethenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(Br)=CC=C1\C=C\S(=O)(=O)N1CCN(C(=O)C2CCN(CC2)C=2C=CN=CC=2)CC1 QXELHDVRNCLCKP-GIJQJNRQSA-N 0.000 claims description 2
WFKWPMGTPYUJLA-VXLYETTFSA-N [4-[(e)-2-(4-methylphenyl)ethenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(C)=CC=C1\C=C\S(=O)(=O)N1CCN(C(=O)C2CCN(CC2)C=2C=CN=CC=2)CC1 WFKWPMGTPYUJLA-VXLYETTFSA-N 0.000 claims description 2
HLVZSJKXAWECLB-VXLYETTFSA-N [4-[(e)-2-phenylethenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)\C=C\C=2C=CC=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 HLVZSJKXAWECLB-VXLYETTFSA-N 0.000 claims description 2
MGWWPUFGSZYBEH-UHFFFAOYSA-N [4-[4-(4-bromophenyl)phenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(Br)=CC=C1C1=CC=C(S(=O)(=O)N2CCN(CC2)C(=O)C2CCN(CC2)C=2C=CN=CC=2)C=C1 MGWWPUFGSZYBEH-UHFFFAOYSA-N 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 2
238000003776 cleavage reaction Methods 0.000 claims description 2
125000005265 dialkylamine group Chemical group 0.000 claims description 2
AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical group FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 2
125000002346 iodo group Chemical group I* 0.000 claims description 2
239000012948 isocyanate Substances 0.000 claims description 2
150000002513 isocyanates Chemical class 0.000 claims description 2
FRRSCFKBYSAQDN-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 FRRSCFKBYSAQDN-UHFFFAOYSA-N 0.000 claims description 2
VHWURLZUIYFPRA-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxo-3-piperidin-1-ylpropyl]-2-(1-pyridin-4-ylpiperidin-4-yl)acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)CC(CC1)CCN1C1=CC=NC=C1 VHWURLZUIYFPRA-UHFFFAOYSA-N 0.000 claims description 2
VBYIVPZYCNKFFD-UHFFFAOYSA-N n-fluorohydroxylamine Chemical group ONF VBYIVPZYCNKFFD-UHFFFAOYSA-N 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
230000007017 scission Effects 0.000 claims description 2
101100001672 Emericella variicolor andG gene Proteins 0.000 claims 1
ZLAKCKVFSRSENR-UHFFFAOYSA-N [4-(6-chloro-naphthalene-2-sulfonyl)-piperazin-1-yl]-(3,4,5,6-tetrahydro-2h-[1,4']bipyridinyl-4-yl)-methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 ZLAKCKVFSRSENR-UHFFFAOYSA-N 0.000 claims 1
OZSPNUWKLVGHJT-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)N(CC1)CCN1C1=CC=NC=C1 OZSPNUWKLVGHJT-UHFFFAOYSA-N 0.000 claims 1
BLNIAOKBISRBLC-GIJQJNRQSA-N [4-[(e)-2-(4-fluorophenyl)ethenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(F)=CC=C1\C=C\S(=O)(=O)N1CCN(C(=O)C2CCN(CC2)C=2C=CN=CC=2)CC1 BLNIAOKBISRBLC-GIJQJNRQSA-N 0.000 claims 1
230000007306 turnover Effects 0.000 claims 1
125000005843 halogen group Chemical group 0.000 abstract description 25
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract 1
102100024854 Taste receptor type 2 member 4 Human genes 0.000 abstract 1
108050000632 Taste receptor type 2 member 4 Proteins 0.000 abstract 1
239000000203 mixture Substances 0.000 description 387
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 360
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 314
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 152
229910001868 water Inorganic materials 0.000 description 139
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 130
239000000243 solution Substances 0.000 description 116
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
235000019439 ethyl acetate Nutrition 0.000 description 105
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 76
238000000921 elemental analysis Methods 0.000 description 73
239000012074 organic phase Substances 0.000 description 71
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
238000004440 column chromatography Methods 0.000 description 63
239000003480 eluent Substances 0.000 description 62
239000000463 material Substances 0.000 description 58
238000005481 NMR spectroscopy Methods 0.000 description 44
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
238000012360 testing method Methods 0.000 description 40
239000000047 product Substances 0.000 description 36
239000012258 stirred mixture Substances 0.000 description 33
NBHZSEHHFDGJEZ-UHFFFAOYSA-N 1-pyridin-4-ylpiperidine-4-carbonyl chloride Chemical compound C1CC(C(=O)Cl)CCN1C1=CC=NC=C1 NBHZSEHHFDGJEZ-UHFFFAOYSA-N 0.000 description 31
OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 26
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
108010074860 Factor Xa Proteins 0.000 description 23
239000002244 precipitate Substances 0.000 description 23
239000007787 solid Substances 0.000 description 23
239000012267 brine Substances 0.000 description 22
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 22
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
238000000746 purification Methods 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
OQZBAQXTXNIPRA-UHFFFAOYSA-N 1-pyridin-4-ylpiperazine Chemical compound C1CNCCN1C1=CC=NC=C1 OQZBAQXTXNIPRA-UHFFFAOYSA-N 0.000 description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
239000003054 catalyst Substances 0.000 description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
239000000706 filtrate Substances 0.000 description 15
239000006260 foam Substances 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
239000012298 atmosphere Substances 0.000 description 13
239000002585 base Substances 0.000 description 13
239000003921 oil Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
239000000725 suspension Substances 0.000 description 12
108090000190 Thrombin Proteins 0.000 description 11
125000002252 acyl group Chemical group 0.000 description 11
125000004076 pyridyl group Chemical group 0.000 description 11
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 11
238000011282 treatment Methods 0.000 description 11
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
208000007536 Thrombosis Diseases 0.000 description 10
230000015271 coagulation Effects 0.000 description 10
238000005345 coagulation Methods 0.000 description 10
229960004072 thrombin Drugs 0.000 description 10
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
MTFDMQASMMCFHB-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)acetic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCC(=O)O)=CC=C21 MTFDMQASMMCFHB-UHFFFAOYSA-N 0.000 description 9
239000007789 gas Substances 0.000 description 9
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
238000001990 intravenous administration Methods 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
125000001544 thienyl group Chemical group 0.000 description 9
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
125000002971 oxazolyl group Chemical group 0.000 description 8
125000000714 pyrimidinyl group Chemical group 0.000 description 8
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
CUQXSBQSPHOSCK-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-piperidin-4-ylmethanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C1CCNCC1 CUQXSBQSPHOSCK-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 7
125000000335 thiazolyl group Chemical group 0.000 description 7
IYFIYGSJZIICOZ-UHFFFAOYSA-N 6-chloronaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=CC(Cl)=CC=C21 IYFIYGSJZIICOZ-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
239000006185 dispersion Substances 0.000 description 6
239000003701 inert diluent Substances 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
239000002480 mineral oil Substances 0.000 description 6
235000010446 mineral oil Nutrition 0.000 description 6
KTXCOBVGGZETQY-UHFFFAOYSA-N piperazin-1-yl-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CNCCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 KTXCOBVGGZETQY-UHFFFAOYSA-N 0.000 description 6
125000003226 pyrazolyl group Chemical group 0.000 description 6
238000010992 reflux Methods 0.000 description 6
JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 5
HBZJVDNETONGIS-UHFFFAOYSA-N 4-chloropyrimidine;hydrochloride Chemical compound Cl.ClC1=CC=NC=N1 HBZJVDNETONGIS-UHFFFAOYSA-N 0.000 description 5
101100167280 Caenorhabditis elegans cin-4 gene Proteins 0.000 description 5
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
108091005804 Peptidases Proteins 0.000 description 5
239000004365 Protease Substances 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000000284 extract Substances 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
239000010410 layer Substances 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 5
HLGOZTPBXXVTEQ-UHFFFAOYSA-N (4-aminophenyl)-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CCN(C=2C=CN=CC=2)CC1 HLGOZTPBXXVTEQ-UHFFFAOYSA-N 0.000 description 4
WDBQAIDRONYXLD-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-1-yl)-piperidin-4-ylmethanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C1CCNCC1 WDBQAIDRONYXLD-UHFFFAOYSA-N 0.000 description 4
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 4
WWRPVOCMZXEUBU-UHFFFAOYSA-N 1-(4-iodophenyl)sulfonylpiperazine Chemical compound C1=CC(I)=CC=C1S(=O)(=O)N1CCNCC1 WWRPVOCMZXEUBU-UHFFFAOYSA-N 0.000 description 4
NYKJBLCQSRULIL-UHFFFAOYSA-N 2-(4-pyridin-4-ylpiperazin-1-yl)acetyl chloride Chemical compound C1CN(CC(=O)Cl)CCN1C1=CC=NC=C1 NYKJBLCQSRULIL-UHFFFAOYSA-N 0.000 description 4
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
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 4
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
125000003435 aroyl group Chemical group 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
230000008021 deposition Effects 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
IAEHFMBLCHNXJS-UHFFFAOYSA-N ethyl 1-benzylpiperazine-2-carboxylate Chemical compound CCOC(=O)C1CNCCN1CC1=CC=CC=C1 IAEHFMBLCHNXJS-UHFFFAOYSA-N 0.000 description 4
RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 4
239000011521 glass Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
TZABGKWGXRIVOZ-UHFFFAOYSA-N n-(2-amino-3-oxo-3-piperidin-1-ylpropyl)-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1CCCCN1C(=O)C(N)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 TZABGKWGXRIVOZ-UHFFFAOYSA-N 0.000 description 4
AIJUKEFFHUGWLZ-UHFFFAOYSA-N n-(2-aminoethyl)-2-(naphthalen-2-ylsulfonylamino)acetamide;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(S(=O)(=O)NCC(=O)NCCN)=CC=C21 AIJUKEFFHUGWLZ-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
UYINAURTFKCHDW-UHFFFAOYSA-N (3-aminopyrrolidin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone;hydrochloride Chemical compound Cl.C1C(N)CCN1C(=O)C1CCN(C=2C=CN=CC=2)CC1 UYINAURTFKCHDW-UHFFFAOYSA-N 0.000 description 3
HVBRPCXLQIUQLT-AATRIKPKSA-N (e)-2-(4-chlorophenyl)ethenesulfonyl chloride Chemical compound ClC1=CC=C(\C=C\S(Cl)(=O)=O)C=C1 HVBRPCXLQIUQLT-AATRIKPKSA-N 0.000 description 3
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
FTCPGPDEZQVGND-UHFFFAOYSA-N 1-(naphthalen-2-ylmethyl)piperazin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1CNCCN1CC1=CC=C(C=CC=C2)C2=C1 FTCPGPDEZQVGND-UHFFFAOYSA-N 0.000 description 3
FNQCPLLODQSVDV-UHFFFAOYSA-N 1-[4-(4-methylphenyl)phenyl]sulfonylpiperazine Chemical compound C1=CC(C)=CC=C1C1=CC=C(S(=O)(=O)N2CCNCC2)C=C1 FNQCPLLODQSVDV-UHFFFAOYSA-N 0.000 description 3
IBYGHOPTTMPJBR-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonylpiperazine;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N1CCNCC1 IBYGHOPTTMPJBR-UHFFFAOYSA-N 0.000 description 3
KTQWWYGLWQVHDM-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonylpiperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 KTQWWYGLWQVHDM-UHFFFAOYSA-N 0.000 description 3
MDJITYWHEVEXJY-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonylpiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 MDJITYWHEVEXJY-UHFFFAOYSA-N 0.000 description 3
SHXRWWBRVGRDOV-UHFFFAOYSA-N 1-piperazin-1-yl-2-(4-pyridin-4-ylpiperazin-1-yl)ethanone Chemical compound C1CNCCN1C(=O)CN(CC1)CCN1C1=CC=NC=C1 SHXRWWBRVGRDOV-UHFFFAOYSA-N 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
MRMJBEVGTAYFBF-UHFFFAOYSA-N 2-(1-pyridin-4-ylpiperidin-4-yl)acetyl chloride;hydrochloride Chemical compound Cl.C1CC(CC(=O)Cl)CCN1C1=CC=NC=C1 MRMJBEVGTAYFBF-UHFFFAOYSA-N 0.000 description 3
LYVWBHUMNIXHEG-UHFFFAOYSA-N 2-amino-1-piperidin-1-yl-5-(4-pyridin-4-ylpiperazin-1-yl)pentane-1,5-dione Chemical compound C1CCCCN1C(=O)C(N)CCC(=O)N(CC1)CCN1C1=CC=NC=C1 LYVWBHUMNIXHEG-UHFFFAOYSA-N 0.000 description 3
IXZIREMUFHMAAQ-UHFFFAOYSA-N 2-benzyl-1-naphthalen-2-ylsulfonylpiperazine Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N1CCNCC1CC1=CC=CC=C1 IXZIREMUFHMAAQ-UHFFFAOYSA-N 0.000 description 3
JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 3
MPOQBMWVIZOLLG-UHFFFAOYSA-N 4-(6-bromonaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Br)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 MPOQBMWVIZOLLG-UHFFFAOYSA-N 0.000 description 3
FYDIJVOISYUTEU-UHFFFAOYSA-N 4-(6-chloronaphthalen-2-yl)sulfonyl-2-(4-nitrophenyl)piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1C1=CC=C([N+]([O-])=O)C=C1 FYDIJVOISYUTEU-UHFFFAOYSA-N 0.000 description 3
TUUFZKVVTGDCOW-UHFFFAOYSA-N 4-naphthalen-2-ylsulfanylpiperidine Chemical compound C1CNCCC1SC1=CC=C(C=CC=C2)C2=C1 TUUFZKVVTGDCOW-UHFFFAOYSA-N 0.000 description 3
VHKVWXNTBIDEEF-UHFFFAOYSA-N 4-naphthalen-2-ylsulfonylpiperidine Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)C1CCNCC1 VHKVWXNTBIDEEF-UHFFFAOYSA-N 0.000 description 3
SEMRCUIXRUXGJX-UHFFFAOYSA-N 6-aminonaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(N)=CC=C21 SEMRCUIXRUXGJX-UHFFFAOYSA-N 0.000 description 3
RDKORFDRILIBOL-UHFFFAOYSA-N 6-bromonaphthalene-2-sulfonyl chloride Chemical compound C1=C(Br)C=CC2=CC(S(=O)(=O)Cl)=CC=C21 RDKORFDRILIBOL-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
229940123583 Factor Xa inhibitor Drugs 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
108010000499 Thromboplastin Proteins 0.000 description 3
102000002262 Thromboplastin Human genes 0.000 description 3
239000013543 active substance Substances 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
230000023555 blood coagulation Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 3
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 3
238000001816 cooling Methods 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
201000010099 disease Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000006196 drop Substances 0.000 description 3
LPSRKUNQINELGQ-UHFFFAOYSA-N ethyl 2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propanoate Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)OCC)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 LPSRKUNQINELGQ-UHFFFAOYSA-N 0.000 description 3
YDXOADIIALXRTP-UHFFFAOYSA-N ethyl 2-amino-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propanoate;dihydrochloride Chemical compound Cl.Cl.C1CC(C(=O)NCC(N)C(=O)OCC)CCN1C1=CC=NC=C1 YDXOADIIALXRTP-UHFFFAOYSA-N 0.000 description 3
LUUZKNFUMJLVSU-UHFFFAOYSA-N ethyl 4-naphthalen-2-ylsulfonylpiperazine-2-carboxylate Chemical compound C1CNC(C(=O)OCC)CN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 LUUZKNFUMJLVSU-UHFFFAOYSA-N 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
125000001041 indolyl group Chemical group 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
125000005956 isoquinolyl group Chemical group 0.000 description 3
125000001786 isothiazolyl group Chemical group 0.000 description 3
125000000842 isoxazolyl group Chemical group 0.000 description 3
238000005259 measurement Methods 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
KFXHSDXGIICXMF-UHFFFAOYSA-N methyl 2-(1-naphthalen-2-ylsulfonylpiperazin-2-yl)acetate Chemical compound COC(=O)CC1CNCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 KFXHSDXGIICXMF-UHFFFAOYSA-N 0.000 description 3
QOSDGAQRGMJGNQ-UHFFFAOYSA-N methyl 4-(6-chloronaphthalen-2-yl)sulfonyl-1-(piperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound COC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C1CCNCC1 QOSDGAQRGMJGNQ-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
PDJUECNQPIBZCD-UHFFFAOYSA-N n-(2-amino-3-phenylpropyl)-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=CC=CC=1CC(N)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 PDJUECNQPIBZCD-UHFFFAOYSA-N 0.000 description 3
MDNJNIXQHVNFMH-UHFFFAOYSA-N n-(3-amino-1-oxo-1-piperidin-1-ylpropan-2-yl)naphthalene-2-sulfonamide;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC(CN)C(=O)N1CCCCC1 MDNJNIXQHVNFMH-UHFFFAOYSA-N 0.000 description 3
NOJZQFXDTWGIAB-UHFFFAOYSA-N n-piperidin-4-ylnaphthalene-2-sulfonamide;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NC1CCNCC1 NOJZQFXDTWGIAB-UHFFFAOYSA-N 0.000 description 3
125000001715 oxadiazolyl group Chemical group 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
WBEZBLCJGASOIU-UHFFFAOYSA-N piperidin-4-yl-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1CN(C=2C=CN=CC=2)CCN1C(=O)C1CCNCC1 WBEZBLCJGASOIU-UHFFFAOYSA-N 0.000 description 3
230000002265 prevention Effects 0.000 description 3
125000000168 pyrrolyl group Chemical group 0.000 description 3
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
125000005493 quinolyl group Chemical group 0.000 description 3
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
JGGFVSGYTHUAOQ-UHFFFAOYSA-M sodium;naphthalene-2-sulfinate Chemical compound [Na+].C1=CC=CC2=CC(S(=O)[O-])=CC=C21 JGGFVSGYTHUAOQ-UHFFFAOYSA-M 0.000 description 3
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
125000001113 thiadiazolyl group Chemical group 0.000 description 3
QMHSQYCZYKWYFS-UHFFFAOYSA-N tributyl-(4-piperazin-1-ylsulfonylphenyl)stannane Chemical compound C1=CC([Sn](CCCC)(CCCC)CCCC)=CC=C1S(=O)(=O)N1CCNCC1 QMHSQYCZYKWYFS-UHFFFAOYSA-N 0.000 description 3
FGBXHGWWTCLCNK-UHFFFAOYSA-N (3-methylpiperazin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CNC(C)CN1C(=O)C1CCN(C=2C=CN=CC=2)CC1 FGBXHGWWTCLCNK-UHFFFAOYSA-N 0.000 description 2
XBIPGYODDSJAFQ-KRWDZBQOSA-N (3s)-3-(naphthalen-2-ylsulfonylamino)-4-oxo-4-piperidin-1-ylbutanoic acid Chemical compound O=C([C@@H](NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC(=O)O)N1CCCCC1 XBIPGYODDSJAFQ-KRWDZBQOSA-N 0.000 description 2
MPCHVBWJRPGWHL-SFHVURJKSA-N (3s)-3-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-4-oxo-4-piperidin-1-ylbutanoic acid Chemical compound O=C([C@@H](NC(=O)CNS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC(=O)O)N1CCCCC1 MPCHVBWJRPGWHL-SFHVURJKSA-N 0.000 description 2
LLIWZYCJAHCYDI-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-2-yl)methanol Chemical compound C1CNC(CO)CN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 LLIWZYCJAHCYDI-UHFFFAOYSA-N 0.000 description 2
PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 2
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
CUSGSDUYPXBYHI-UHFFFAOYSA-N 1,3-dibenzylpiperazine-2,5-dione Chemical compound O=C1C(CC=2C=CC=CC=2)NC(=O)CN1CC1=CC=CC=C1 CUSGSDUYPXBYHI-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
HFVJTQOHBQUGTR-UHFFFAOYSA-N 1-(3-bromophenyl)sulfonylpiperazine Chemical compound BrC1=CC=CC(S(=O)(=O)N2CCNCC2)=C1 HFVJTQOHBQUGTR-UHFFFAOYSA-N 0.000 description 2
RHDYXTLQDAMLKN-UHFFFAOYSA-N 1-(4-pyridin-2-ylphenyl)sulfonylpiperazine Chemical compound C=1C=C(C=2N=CC=CC=2)C=CC=1S(=O)(=O)N1CCNCC1 RHDYXTLQDAMLKN-UHFFFAOYSA-N 0.000 description 2
PUWJXVNBKNHYTQ-UHFFFAOYSA-N 1-(6-chloronaphthalen-2-yl)sulfonylpiperazine;hydrochloride Chemical compound Cl.C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N1CCNCC1 PUWJXVNBKNHYTQ-UHFFFAOYSA-N 0.000 description 2
NANQJUFFKXWVJR-UHFFFAOYSA-N 1-(benzenesulfonyl)piperazine Chemical compound C=1C=CC=CC=1S(=O)(=O)N1CCNCC1 NANQJUFFKXWVJR-UHFFFAOYSA-N 0.000 description 2
RNIUAVHPKJDEMZ-RMKNXTFCSA-N 1-[(e)-2-(4-chlorophenyl)ethenyl]sulfonyl-3-methylpiperazine Chemical compound C1CNC(C)CN1S(=O)(=O)\C=C\C1=CC=C(Cl)C=C1 RNIUAVHPKJDEMZ-RMKNXTFCSA-N 0.000 description 2
LHRLVWCLGLXWSL-UHFFFAOYSA-N 1-[3-(3,5-dichlorophenyl)phenyl]sulfonylpiperazine Chemical compound ClC1=CC(Cl)=CC(C=2C=C(C=CC=2)S(=O)(=O)N2CCNCC2)=C1 LHRLVWCLGLXWSL-UHFFFAOYSA-N 0.000 description 2
VMGJYXNHLXSTTD-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonyl-1,4-diazepane Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N1CCCNCC1 VMGJYXNHLXSTTD-UHFFFAOYSA-N 0.000 description 2
HYTAUHBGWKZSOO-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonyl-4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylic acid Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(C(=O)O)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 HYTAUHBGWKZSOO-UHFFFAOYSA-N 0.000 description 2
URTPNQRAHXRPMP-UHFFFAOYSA-N 1-phenylmethoxycarbonylpiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(=O)OCC1=CC=CC=C1 URTPNQRAHXRPMP-UHFFFAOYSA-N 0.000 description 2
UISWRUUBFFHGLE-UHFFFAOYSA-N 1-pyridin-1-ium-4-ylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)O)CCN1C1=CC=NC=C1 UISWRUUBFFHGLE-UHFFFAOYSA-N 0.000 description 2
YIIPGCJYIQXQKU-UHFFFAOYSA-N 2,5-dimethyl-1-naphthalen-2-ylsulfonylpiperazine Chemical compound CC1CNC(C)CN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 YIIPGCJYIQXQKU-UHFFFAOYSA-N 0.000 description 2
SKQQZDXQBQHYEJ-UHFFFAOYSA-N 2-(4-pyridin-4-ylpiperazin-1-yl)acetic acid Chemical compound C1CN(CC(=O)O)CCN1C1=CC=NC=C1 SKQQZDXQBQHYEJ-UHFFFAOYSA-N 0.000 description 2
DSOQMSYNBSAEGG-UHFFFAOYSA-N 2-[(6-chloronaphthalen-2-yl)sulfonylamino]acetic acid Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)NCC(=O)O)=CC=C21 DSOQMSYNBSAEGG-UHFFFAOYSA-N 0.000 description 2
FZFDDSNLQXLBMP-UHFFFAOYSA-N 2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propanoic acid Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)O)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 FZFDDSNLQXLBMP-UHFFFAOYSA-N 0.000 description 2
NPTGVVKPLWFPPX-UHFFFAOYSA-N 2-amino-4-chloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(N)=N1 NPTGVVKPLWFPPX-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
PJGOLCXVWIYXRQ-UHFFFAOYSA-N 3-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC(Br)=C1 PJGOLCXVWIYXRQ-UHFFFAOYSA-N 0.000 description 2
XZWFISGWJBCHBE-UHFFFAOYSA-N 3-methyl-1-naphthalen-2-ylsulfonylpiperazine Chemical compound C1CNC(C)CN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 XZWFISGWJBCHBE-UHFFFAOYSA-N 0.000 description 2
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
SSBVDUAYXSMLTR-UHFFFAOYSA-N 4-(4-bromophenyl)benzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=C(Br)C=C1 SSBVDUAYXSMLTR-UHFFFAOYSA-N 0.000 description 2
CPYFXXWHNKSBRR-UHFFFAOYSA-N 4-(4-chlorophenyl)benzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=C(Cl)C=C1 CPYFXXWHNKSBRR-UHFFFAOYSA-N 0.000 description 2
NWYUSJMIHFIMTA-UHFFFAOYSA-N 4-(4-chlorophenyl)benzenesulfonyl chloride Chemical compound C1=CC(Cl)=CC=C1C1=CC=C(S(Cl)(=O)=O)C=C1 NWYUSJMIHFIMTA-UHFFFAOYSA-N 0.000 description 2
PKRVKIZPJPPOED-UHFFFAOYSA-N 4-(naphthalen-2-ylsulfonylamino)butanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCCCC(=O)O)=CC=C21 PKRVKIZPJPPOED-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 2
OEEUUEUJPBMLFN-UHFFFAOYSA-N 4-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]butanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCC(=O)NCCCC(=O)O)=CC=C21 OEEUUEUJPBMLFN-UHFFFAOYSA-N 0.000 description 2
DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
SPPHJFFCZWZHAY-UHFFFAOYSA-N 6-fluoronaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=CC(F)=CC=C21 SPPHJFFCZWZHAY-UHFFFAOYSA-N 0.000 description 2
QYCDJXYAIDWYFK-UHFFFAOYSA-N 6-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=CC(OC)=CC=C21 QYCDJXYAIDWYFK-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
206010053567 Coagulopathies Diseases 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
108010094028 Prothrombin Proteins 0.000 description 2
102100027378 Prothrombin Human genes 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
CJTROZUPKBGMBC-UHFFFAOYSA-N [4-(6-bromonaphthalen-2-yl)sulfonyl-2-(morpholine-4-carbonyl)piperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC2=CC(Br)=CC=C2C=C1S(=O)(=O)N(C1)CCN(C(=O)C2CCN(CC2)C=2C=CN=CC=2)C1C(=O)N1CCOCC1 CJTROZUPKBGMBC-UHFFFAOYSA-N 0.000 description 2
AXYOIAYIGMFQML-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(1-pyrimidin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NC=N1 AXYOIAYIGMFQML-UHFFFAOYSA-N 0.000 description 2
IMJNFGYISSTOBK-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-[1-(4,6-dichloro-1,3,5-triazin-2-yl)piperidin-4-yl]methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=NC(Cl)=NC(Cl)=N1 IMJNFGYISSTOBK-UHFFFAOYSA-N 0.000 description 2
DXQROAKUXYKYLO-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-[1-(5,6-dichloropyridazin-4-yl)piperidin-4-yl]methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CN=NC(Cl)=C1Cl DXQROAKUXYKYLO-UHFFFAOYSA-N 0.000 description 2
NGLFKYVCCUVTBP-LICLKQGHSA-N [4-[(e)-2-(4-chlorophenyl)ethenyl]sulfonyl-2-methylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound CC1CN(S(=O)(=O)\C=C\C=2C=CC(Cl)=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 NGLFKYVCCUVTBP-LICLKQGHSA-N 0.000 description 2
ZCJAJHPSGDZFFW-LZYBPNLTSA-N [4-[(e)-2-(4-chlorophenyl)ethenyl]sulfonylpiperazin-1-yl]-(1-pyrimidin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(Cl)=CC=C1\C=C\S(=O)(=O)N1CCN(C(=O)C2CCN(CC2)C=2N=CN=CC=2)CC1 ZCJAJHPSGDZFFW-LZYBPNLTSA-N 0.000 description 2
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
229940127219 anticoagulant drug Drugs 0.000 description 2
125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
125000005002 aryl methyl group Chemical group 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
WWGBHSKNFUXNJZ-UHFFFAOYSA-N benzyl n-(3-amino-1-oxo-1-piperidin-1-ylpropan-2-yl)carbamate Chemical compound C1CCCCN1C(=O)C(CN)NC(=O)OCC1=CC=CC=C1 WWGBHSKNFUXNJZ-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
208000026106 cerebrovascular disease Diseases 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000010949 copper Substances 0.000 description 2
229910052802 copper Inorganic materials 0.000 description 2
210000004351 coronary vessel Anatomy 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
125000004988 dibenzothienyl group Chemical group C1(=CC=CC=2SC3=C(C21)C=CC=C3)* 0.000 description 2
229940079593 drug Drugs 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
GWJGJLJJARHIEU-UHFFFAOYSA-N ethyl 1-benzyl-4-naphthalen-2-ylsulfonylpiperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1CC1=CC=CC=C1 GWJGJLJJARHIEU-UHFFFAOYSA-N 0.000 description 2
BQGVAWQYLWRSMD-UHFFFAOYSA-N ethyl 1-naphthalen-2-ylsulfonyl-4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(C(=O)OCC)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 BQGVAWQYLWRSMD-UHFFFAOYSA-N 0.000 description 2
WFFNRMTWMDBKDZ-UHFFFAOYSA-N ethyl 3-amino-2-(phenylmethoxycarbonylamino)propanoate;hydrochloride Chemical compound Cl.CCOC(=O)C(CN)NC(=O)OCC1=CC=CC=C1 WFFNRMTWMDBKDZ-UHFFFAOYSA-N 0.000 description 2
DYQDLMSELXMBLB-UHFFFAOYSA-N ethyl 4-(4-piperazin-1-ylsulfonylphenyl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=C(S(=O)(=O)N2CCNCC2)C=C1 DYQDLMSELXMBLB-UHFFFAOYSA-N 0.000 description 2
MLFFGILBOPYZGU-UHFFFAOYSA-N ethyl 4-(6-bromonaphthalen-2-yl)sulfonylpiperazine-2-carboxylate Chemical compound C1CNC(C(=O)OCC)CN1S(=O)(=O)C1=CC=C(C=C(Br)C=C2)C2=C1 MLFFGILBOPYZGU-UHFFFAOYSA-N 0.000 description 2
AMFBWMFNBYSOKB-UHFFFAOYSA-N ethyl 4-(6-chloronaphthalen-2-yl)sulfonylpiperazine-2-carboxylate Chemical compound C1CNC(C(=O)OCC)CN1S(=O)(=O)C1=CC=C(C=C(Cl)C=C2)C2=C1 AMFBWMFNBYSOKB-UHFFFAOYSA-N 0.000 description 2
238000009472 formulation Methods 0.000 description 2
125000003838 furazanyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
KVQGGLZHHFGHPU-UHFFFAOYSA-N methyl 4-aminobutanoate Chemical compound COC(=O)CCCN KVQGGLZHHFGHPU-UHFFFAOYSA-N 0.000 description 2
YMPHTJJCMUUJRK-UHFFFAOYSA-N n-(2-amino-3-oxo-3-piperidin-1-ylpropyl)-2-(naphthalen-2-ylsulfonylamino)acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCC(N)C(=O)N1CCCCC1 YMPHTJJCMUUJRK-UHFFFAOYSA-N 0.000 description 2
XGYRFXBHCUVFFQ-UHFFFAOYSA-N n-(3-aminopropyl)naphthalene-2-sulfonamide Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCCCN)=CC=C21 XGYRFXBHCUVFFQ-UHFFFAOYSA-N 0.000 description 2
ABHOAVLCVLRMLD-UHFFFAOYSA-N n-(4-amino-1-oxo-1-piperidin-1-ylbutan-2-yl)-2-(naphthalen-2-ylsulfonylamino)acetamide;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CCN)C(=O)N1CCCCC1 ABHOAVLCVLRMLD-UHFFFAOYSA-N 0.000 description 2
XYIJWHIRZSGDDY-UHFFFAOYSA-N n-[2-[(2-aminoacetyl)amino]-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1CCCCN1C(=O)C(NC(=O)CN)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 XYIJWHIRZSGDDY-UHFFFAOYSA-N 0.000 description 2
IEZOVXPRSWTNJA-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethyl]piperidine-4-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCCNC(=O)C1CCNCC1 IEZOVXPRSWTNJA-UHFFFAOYSA-N 0.000 description 2
230000014508 negative regulation of coagulation Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
IQWBXSUUWQJNFK-UHFFFAOYSA-N piperazin-1-yl-(1-pyridin-4-ylpiperidin-4-yl)methanone;trihydrochloride Chemical compound Cl.Cl.Cl.C1CNCCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 IQWBXSUUWQJNFK-UHFFFAOYSA-N 0.000 description 2
210000002381 plasma Anatomy 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
125000004742 propyloxycarbonyl group Chemical group 0.000 description 2
229940039716 prothrombin Drugs 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
125000002098 pyridazinyl group Chemical group 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
239000012047 saturated solution Substances 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
239000000377 silicon dioxide Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
238000003860 storage Methods 0.000 description 2
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 2
229910052717 sulfur Chemical group 0.000 description 2
239000011593 sulfur Chemical group 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
FCMLWBBLOASUSO-UHFFFAOYSA-N tert-butyl 3-oxopiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(=O)C1 FCMLWBBLOASUSO-UHFFFAOYSA-N 0.000 description 2
WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
LHZRJEOMDFKIJM-UHFFFAOYSA-N tert-butyl n-(1-amino-3-phenylpropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(CN)CC1=CC=CC=C1 LHZRJEOMDFKIJM-UHFFFAOYSA-N 0.000 description 2
KBOCLXOFXRIEFX-UHFFFAOYSA-N tert-butyl n-(3-amino-4-oxo-4-piperidin-1-ylbutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC(N)C(=O)N1CCCCC1 KBOCLXOFXRIEFX-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
GXWVRNFRGOSMCE-UHFFFAOYSA-N (1-naphthalen-2-ylsulfonylpiperidin-3-yl)-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1CCN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC1C(=O)N(CC1)CCN1C1=CC=NC=C1 GXWVRNFRGOSMCE-UHFFFAOYSA-N 0.000 description 1
YNBIYOADYCFNJY-UHFFFAOYSA-N (1-pyridin-4-ylpiperidin-4-yl)-[4-(5-pyridin-2-ylthiophen-2-yl)sulfonylpiperazin-1-yl]methanone Chemical compound C1CN(S(=O)(=O)C=2SC(=CC=2)C=2N=CC=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 YNBIYOADYCFNJY-UHFFFAOYSA-N 0.000 description 1
VCQURUZYYSOUHP-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 2,2,2-trifluoroacetate Chemical compound FC1=C(F)C(F)=C(OC(=O)C(F)(F)F)C(F)=C1F VCQURUZYYSOUHP-UHFFFAOYSA-N 0.000 description 1
ZDCIHNWVXROPMN-UHFFFAOYSA-N (2,4,5-trichlorophenyl) carbonochloridate Chemical compound ClC(=O)OC1=CC(Cl)=C(Cl)C=C1Cl ZDCIHNWVXROPMN-UHFFFAOYSA-N 0.000 description 1
SWYXHEUQGHUUSI-UHFFFAOYSA-N (2,5-dimethyl-4-naphthalen-2-ylsulfonylpiperazin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound CC1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(C)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 SWYXHEUQGHUUSI-UHFFFAOYSA-N 0.000 description 1
PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
YDMBNDUHUNWWRP-VJBWXMMDSA-N (2s)-1-[(2r)-2-amino-3-phenylpropanoyl]-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]piperidine-2-carboxamide Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C1=CC=CC=C1 YDMBNDUHUNWWRP-VJBWXMMDSA-N 0.000 description 1
DKYRKAIKWFHQHM-UHFFFAOYSA-N (3,5-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=CC(Cl)=C1 DKYRKAIKWFHQHM-UHFFFAOYSA-N 0.000 description 1
PCRTXIBTBMKGFY-UHFFFAOYSA-N (3-methyl-4-naphthalen-2-ylsulfonylpiperazin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(C)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 PCRTXIBTBMKGFY-UHFFFAOYSA-N 0.000 description 1
CFPFMAGBHTVLCZ-UHFFFAOYSA-N (4-chlorophenoxy)boronic acid Chemical compound OB(O)OC1=CC=C(Cl)C=C1 CFPFMAGBHTVLCZ-UHFFFAOYSA-N 0.000 description 1
DQVXWCCLFKMJTQ-UHFFFAOYSA-N (4-methylphenoxy)boronic acid Chemical compound CC1=CC=C(OB(O)O)C=C1 DQVXWCCLFKMJTQ-UHFFFAOYSA-N 0.000 description 1
PTJIUDPHIBZFHE-UHFFFAOYSA-N (4-naphthalen-1-ylsulfonylpiperazin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 PTJIUDPHIBZFHE-UHFFFAOYSA-N 0.000 description 1
YAXIXDGJNHWJHG-UHFFFAOYSA-N (4-naphthalen-2-ylsulfanylpiperidin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CC(SC=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 YAXIXDGJNHWJHG-UHFFFAOYSA-N 0.000 description 1
IWILDNKCHYXGLV-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-1-yl)-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)N(CC1)CCN1C1=CC=NC=C1 IWILDNKCHYXGLV-UHFFFAOYSA-N 0.000 description 1
XRSNBYICYIIHRL-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperazin-1-yl)-[1-(1,3,5-triazin-2-yl)piperidin-4-yl]methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=NC=NC=N1 XRSNBYICYIIHRL-UHFFFAOYSA-N 0.000 description 1
JABFSLKJPWBVRP-UHFFFAOYSA-N (4-naphthalen-2-ylsulfonylpiperidin-1-yl)-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CC(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 JABFSLKJPWBVRP-UHFFFAOYSA-N 0.000 description 1
NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
HLAFCBWJAVOFEH-UHFFFAOYSA-N (4-nitrophenyl)-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)N1CCN(C=2C=CN=CC=2)CC1 HLAFCBWJAVOFEH-UHFFFAOYSA-N 0.000 description 1
XIYWQTOSHXQCPM-WOJGMQOQSA-N (e)-2-(4-chlorophenyl)-n-[4-(4-pyridin-4-ylpiperazine-1-carbonyl)phenyl]ethenesulfonamide Chemical compound C1=CC(Cl)=CC=C1\C=C\S(=O)(=O)NC1=CC=C(C(=O)N2CCN(CC2)C=2C=CN=CC=2)C=C1 XIYWQTOSHXQCPM-WOJGMQOQSA-N 0.000 description 1
LKPTXHKOKIAZMH-AATRIKPKSA-N (e)-2-(4-chlorophenyl)ethenesulfinyl chloride Chemical compound ClC1=CC=C(\C=C\S(Cl)=O)C=C1 LKPTXHKOKIAZMH-AATRIKPKSA-N 0.000 description 1
ONWRSBMOCIQLRK-VOTSOKGWSA-N (e)-2-phenylethenesulfonyl chloride Chemical class ClS(=O)(=O)\C=C\C1=CC=CC=C1 ONWRSBMOCIQLRK-VOTSOKGWSA-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
RDJUHLUBPADHNP-UHFFFAOYSA-N 1,2,3,5-tetrahydroxybenzene Chemical compound OC1=CC(O)=C(O)C(O)=C1 RDJUHLUBPADHNP-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
AJNDRRBUHVZNKU-UHFFFAOYSA-N 1,3-dibenzylpiperazine Chemical compound C=1C=CC=CC=1CC(NCC1)CN1CC1=CC=CC=C1 AJNDRRBUHVZNKU-UHFFFAOYSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 1
ILROLYQPRYHHFG-UHFFFAOYSA-N 1-$l^{1}-oxidanylprop-2-en-1-one Chemical group [O]C(=O)C=C ILROLYQPRYHHFG-UHFFFAOYSA-N 0.000 description 1
QQFDAFXFXYQPMO-UHFFFAOYSA-N 1-(2-amino-6-methylpyrimidin-4-yl)-n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethyl]piperidine-4-carboxamide Chemical compound NC1=NC(C)=CC(N2CCC(CC2)C(=O)NCCNC(=O)CNS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)=N1 QQFDAFXFXYQPMO-UHFFFAOYSA-N 0.000 description 1
RMWDKSLFJLKYNM-UHFFFAOYSA-N 1-(4-naphthalen-2-ylsulfonylpiperazin-1-yl)-2-(4-pyridin-4-ylpiperazin-1-yl)ethanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)CN(CC1)CCN1C1=CC=NC=C1 RMWDKSLFJLKYNM-UHFFFAOYSA-N 0.000 description 1
PTXLQDRXJRYYKN-UHFFFAOYSA-N 1-(naphthalen-2-ylmethyl)-4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazin-2-one Chemical compound C1CN(CC=2C=C3C=CC=CC3=CC=2)C(=O)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 PTXLQDRXJRYYKN-UHFFFAOYSA-N 0.000 description 1
MGKVURWTKXXYCP-BJMVGYQFSA-N 1-[(e)-2-(4-chlorophenyl)ethenyl]sulfonylpiperazine Chemical compound C1=CC(Cl)=CC=C1\C=C\S(=O)(=O)N1CCNCC1 MGKVURWTKXXYCP-BJMVGYQFSA-N 0.000 description 1
JXEVIMZVNUGRMA-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)phenyl]sulfonylpiperazine Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC(S(=O)(=O)N2CCNCC2)=C1 JXEVIMZVNUGRMA-UHFFFAOYSA-N 0.000 description 1
FWNPQFAUBNHNBI-UHFFFAOYSA-N 1-[4-(3,5-dichlorophenyl)phenyl]sulfonylpiperazine Chemical compound ClC1=CC(Cl)=CC(C=2C=CC(=CC=2)S(=O)(=O)N2CCNCC2)=C1 FWNPQFAUBNHNBI-UHFFFAOYSA-N 0.000 description 1
VPYONHRFDAQNAD-UHFFFAOYSA-N 1-[4-(4-bromophenyl)phenyl]sulfonylpiperazine Chemical compound C1=CC(Br)=CC=C1C1=CC=C(S(=O)(=O)N2CCNCC2)C=C1 VPYONHRFDAQNAD-UHFFFAOYSA-N 0.000 description 1
VJZUHNNGDOZPGZ-UHFFFAOYSA-N 1-[4-(4-chloro-2-nitrophenyl)phenyl]sulfonylpiperazine Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C1=CC=C(S(=O)(=O)N2CCNCC2)C=C1 VJZUHNNGDOZPGZ-UHFFFAOYSA-N 0.000 description 1
OCCFVNHEAWDNKF-UHFFFAOYSA-N 1-[4-(4-nitrophenyl)phenyl]sulfonylpiperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC=C(S(=O)(=O)N2CCNCC2)C=C1 OCCFVNHEAWDNKF-UHFFFAOYSA-N 0.000 description 1
YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
UKTIMFAJRPSNGR-UHFFFAOYSA-N 1-bromo-4-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1Br UKTIMFAJRPSNGR-UHFFFAOYSA-N 0.000 description 1
PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
OAMFERZVSCXNPO-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound ON1C(=O)CCC1=O.CC(C)(C)OC(=O)NCC(O)=O OAMFERZVSCXNPO-UHFFFAOYSA-N 0.000 description 1
SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 1
OJWPAXRMRPPQBG-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonylpiperazine Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N1CCNCC1 OJWPAXRMRPPQBG-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
MYHJCTUTPIKNAT-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl piperidine-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1 MYHJCTUTPIKNAT-UHFFFAOYSA-N 0.000 description 1
VMBBUKKNEPSHHS-UHFFFAOYSA-N 1-pyridin-4-ylpiperidine-4-carbonyl chloride;hydrochloride Chemical compound Cl.C1CC(C(=O)Cl)CCN1C1=CC=NC=C1 VMBBUKKNEPSHHS-UHFFFAOYSA-N 0.000 description 1
BSMKLKICYMATEN-UHFFFAOYSA-N 1-pyrimidin-4-ylpiperidine-4-carboxylic acid;hydrochloride Chemical compound Cl.C1CC(C(=O)O)CCN1C1=CC=NC=N1 BSMKLKICYMATEN-UHFFFAOYSA-N 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
XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
REYGROFVUDUQDE-UHFFFAOYSA-N 2,4-dibenzyl-1-naphthalen-2-ylsulfonylpiperazine Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N(C(C1)CC=2C=CC=CC=2)CCN1CC1=CC=CC=C1 REYGROFVUDUQDE-UHFFFAOYSA-N 0.000 description 1
NSMWYRLQHIXVAP-UHFFFAOYSA-N 2,5-dimethylpiperazine Chemical compound CC1CNC(C)CN1 NSMWYRLQHIXVAP-UHFFFAOYSA-N 0.000 description 1
HVBRPCXLQIUQLT-UHFFFAOYSA-N 2-(4-chlorophenyl)ethenesulfonyl chloride Chemical compound ClC1=CC=C(C=CS(Cl)(=O)=O)C=C1 HVBRPCXLQIUQLT-UHFFFAOYSA-N 0.000 description 1
RUHJZSZTSCSTCC-UHFFFAOYSA-N 2-(bromomethyl)naphthalene Chemical compound C1=CC=CC2=CC(CBr)=CC=C21 RUHJZSZTSCSTCC-UHFFFAOYSA-N 0.000 description 1
SBXQWVNVFPCNRQ-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)-n-[4-oxo-4-(4-pyridin-4-ylpiperazin-1-yl)butyl]acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCCCC(=O)N(CC1)CCN1C1=CC=NC=C1 SBXQWVNVFPCNRQ-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
RFCQDOVPMUSZMN-UHFFFAOYSA-N 2-Naphthalenethiol Chemical compound C1=CC=CC2=CC(S)=CC=C21 RFCQDOVPMUSZMN-UHFFFAOYSA-N 0.000 description 1
ZYJPUMXJBDHSIF-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-UHFFFAOYSA-N 0.000 description 1
WYMFYJAEFMOGCM-UHFFFAOYSA-N 2-[(6-chloronaphthalen-2-yl)sulfonyl-methylamino]acetic acid Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)N(CC(O)=O)C)=CC=C21 WYMFYJAEFMOGCM-UHFFFAOYSA-N 0.000 description 1
YNNUSGIPVFPVBX-UHFFFAOYSA-N 2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine Chemical compound CN1CCCC1CCOC(C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
JDDAFHUEOVUDFJ-UHFFFAOYSA-N 2-iodobenzonitrile Chemical compound IC1=CC=CC=C1C#N JDDAFHUEOVUDFJ-UHFFFAOYSA-N 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
IYDUFJOXYMLYNM-UHFFFAOYSA-N 2-piperidin-1-ium-4-ylacetic acid;chloride Chemical class [Cl-].OC(=O)CC1CC[NH2+]CC1 IYDUFJOXYMLYNM-UHFFFAOYSA-N 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
GBAOOJAWDCNOGO-UHFFFAOYSA-N 3,4,5-trichloropyridazine Chemical compound ClC1=CN=NC(Cl)=C1Cl GBAOOJAWDCNOGO-UHFFFAOYSA-N 0.000 description 1
NYIBPWGZGSXURD-UHFFFAOYSA-N 3,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1Cl NYIBPWGZGSXURD-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
ZARBMGXIZPSUAL-UHFFFAOYSA-N 3-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCCC(=O)O)=CC=C21 ZARBMGXIZPSUAL-UHFFFAOYSA-N 0.000 description 1
FOXRXVSTFGNURG-UHFFFAOYSA-N 3-azaniumyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound NCC(C(O)=O)NC(=O)OCC1=CC=CC=C1 FOXRXVSTFGNURG-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
125000006192 3-phenylprop-2-enyl group Chemical group [H]\C(=C(\[H])C([H])([H])*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
SWTQFIWJOQGVPM-UHFFFAOYSA-N 4-(4-bromophenyl)-n-[4-(4-pyridin-4-ylpiperazine-1-carbonyl)phenyl]benzenesulfonamide;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1C1=CC=C(S(=O)(=O)NC=2C=CC(=CC=2)C(=O)N2CCN(CC2)C=2C=CN=CC=2)C=C1 SWTQFIWJOQGVPM-UHFFFAOYSA-N 0.000 description 1
YDPKUGXFZRUVHC-UHFFFAOYSA-N 4-(4-piperazin-1-ylsulfonylphenyl)benzonitrile Chemical compound C=1C=C(C=2C=CC(=CC=2)C#N)C=CC=1S(=O)(=O)N1CCNCC1 YDPKUGXFZRUVHC-UHFFFAOYSA-N 0.000 description 1
CNNBCCPENNBXJT-UHFFFAOYSA-N 4-amino-5-oxo-5-piperidin-1-ylpentanamide Chemical compound NC(=O)CCC(N)C(=O)N1CCCCC1 CNNBCCPENNBXJT-UHFFFAOYSA-N 0.000 description 1
FQQBGGLHWYNNAS-UHFFFAOYSA-N 4-chloro-6-methylpyrimidin-2-amine;hydrochloride Chemical compound Cl.CC1=CC(Cl)=NC(N)=N1 FQQBGGLHWYNNAS-UHFFFAOYSA-N 0.000 description 1
FPWNLURCHDRMHC-UHFFFAOYSA-N 4-chlorobiphenyl Chemical group C1=CC(Cl)=CC=C1C1=CC=CC=C1 FPWNLURCHDRMHC-UHFFFAOYSA-N 0.000 description 1
XGAFCCUNHIMIRV-UHFFFAOYSA-N 4-chloropyridine;hydron;chloride Chemical compound Cl.ClC1=CC=NC=C1 XGAFCCUNHIMIRV-UHFFFAOYSA-N 0.000 description 1
YJUNICGNEUEFBH-UHFFFAOYSA-N 4-chloropyrimidin-2-amine;hydrochloride Chemical compound Cl.NC1=NC=CC(Cl)=N1 YJUNICGNEUEFBH-UHFFFAOYSA-N 0.000 description 1
POXFXTSTVWDWIR-UHFFFAOYSA-N 4-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(I)C=C1 POXFXTSTVWDWIR-UHFFFAOYSA-N 0.000 description 1
UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
XKAUHTYMKNNXRD-UHFFFAOYSA-N 4-naphthalen-2-ylsulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 XKAUHTYMKNNXRD-UHFFFAOYSA-N 0.000 description 1
SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
OGOMWPWAEIDEOU-UHFFFAOYSA-N 5-pyridin-2-ylthiophene-2-sulfonyl chloride Chemical compound S1C(S(=O)(=O)Cl)=CC=C1C1=CC=CC=N1 OGOMWPWAEIDEOU-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
ONLHWRHIJDODKO-UHFFFAOYSA-N 6-chloronaphthalene-2-sulfonic acid Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)O)=CC=C21 ONLHWRHIJDODKO-UHFFFAOYSA-N 0.000 description 1
ZEXCZHWVXMIOFB-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(OC)=CC=C21 ZEXCZHWVXMIOFB-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
DIZJRQPMQPLAMD-UHFFFAOYSA-N 8-chloronaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2C(Cl)=CC=CC2=C1 DIZJRQPMQPLAMD-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
206010002388 Angina unstable Diseases 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
206010008088 Cerebral artery embolism Diseases 0.000 description 1
206010008132 Cerebral thrombosis Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
208000005189 Embolism Diseases 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
201000001429 Intracranial Thrombosis Diseases 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
206010038563 Reocclusion Diseases 0.000 description 1
108010039286 S 2238 Proteins 0.000 description 1
108010023197 Streptokinase Proteins 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
229940111979 Thromboxane synthase inhibitor Drugs 0.000 description 1
108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
208000007814 Unstable Angina Diseases 0.000 description 1
208000024248 Vascular System injury Diseases 0.000 description 1
208000012339 Vascular injury Diseases 0.000 description 1
HDDPJSKXGXMDBM-UHFFFAOYSA-N [1-(2-amino-6-methylpyrimidin-4-yl)piperidin-4-yl]-(4-naphthalen-2-ylsulfonylpiperazin-1-yl)methanone Chemical compound NC1=NC(C)=CC(N2CCC(CC2)C(=O)N2CCN(CC2)S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)=N1 HDDPJSKXGXMDBM-UHFFFAOYSA-N 0.000 description 1
DLGHEOOAGMWSBX-UHFFFAOYSA-N [1-(2-amino-6-methylpyrimidin-4-yl)piperidin-4-yl]-[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]methanone Chemical compound NC1=NC(C)=CC(N2CCC(CC2)C(=O)N2CCN(CC2)S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)=N1 DLGHEOOAGMWSBX-UHFFFAOYSA-N 0.000 description 1
LDJNQXGTXRMUEL-UHFFFAOYSA-N [1-(6-bromonaphthalen-2-yl)sulfonylpiperidin-4-yl]-(4-pyridin-4-ylpiperazin-1-yl)methanone Chemical compound C1=CC2=CC(Br)=CC=C2C=C1S(=O)(=O)N(CC1)CCC1C(=O)N(CC1)CCN1C1=CC=NC=C1 LDJNQXGTXRMUEL-UHFFFAOYSA-N 0.000 description 1
ZDCGUDAISNXAMB-UHFFFAOYSA-N [2-(hydroxymethyl)-4-naphthalen-2-ylsulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound OCC1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 ZDCGUDAISNXAMB-UHFFFAOYSA-N 0.000 description 1
GPZVSZRONMSDIA-UHFFFAOYSA-N [4-(4-pyridin-2-ylphenyl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=CC(=CC=2)C=2N=CC=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 GPZVSZRONMSDIA-UHFFFAOYSA-N 0.000 description 1
QRDFCEVXORHWHH-UHFFFAOYSA-N [4-(7-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C=1C2=CC(Cl)=CC=C2C=CC=1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 QRDFCEVXORHWHH-UHFFFAOYSA-N 0.000 description 1
VDQWXJLKCWZAJR-UHFFFAOYSA-N [4-(8-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=C2C(Cl)=CC=CC2=CC=C1S(=O)(=O)N(CC1)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 VDQWXJLKCWZAJR-UHFFFAOYSA-N 0.000 description 1
JQGYMEAWMNIJGR-UHFFFAOYSA-N [4-[4-(4-chlorophenyl)phenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(Cl)=CC=C1C1=CC=C(S(=O)(=O)N2CCN(CC2)C(=O)C2CCN(CC2)C=2C=CN=CC=2)C=C1 JQGYMEAWMNIJGR-UHFFFAOYSA-N 0.000 description 1
OPBQRJVHNLLJOX-UHFFFAOYSA-N [4-[4-(4-methylphenyl)phenyl]sulfonylpiperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1=CC(C)=CC=C1C1=CC=C(S(=O)(=O)N2CCN(CC2)C(=O)C2CCN(CC2)C=2C=CN=CC=2)C=C1 OPBQRJVHNLLJOX-UHFFFAOYSA-N 0.000 description 1
KYYYGOCTRDTEAH-UHFFFAOYSA-N [4-naphthalen-2-ylsulfonyl-3-(piperidine-1-carbonyl)piperazin-1-yl]-(1-pyridin-4-ylpiperidin-4-yl)methanone Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(C(=O)N2CCCCC2)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 KYYYGOCTRDTEAH-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
150000001264 acyl cyanides Chemical class 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000002399 angioplasty Methods 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000002506 anticoagulant protein Substances 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000003524 antilipemic agent Substances 0.000 description 1
229940127218 antiplatelet drug Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
ZCSQDAZJFOVUIJ-DEOSSOPVSA-N benzyl (3s)-3-(naphthalen-2-ylsulfonylamino)-4-oxo-4-piperidin-1-ylbutanoate Chemical compound O=C([C@@H](NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC(=O)OCC=1C=CC=CC=1)N1CCCCC1 ZCSQDAZJFOVUIJ-DEOSSOPVSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
SLZZGGAALIJEEH-UHFFFAOYSA-N benzyl n-[1,5-dioxo-1-piperidin-1-yl-5-(4-pyridin-4-ylpiperazin-1-yl)pentan-2-yl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)N1CCCCC1)CCC(=O)N(CC1)CCN1C1=CC=NC=C1 SLZZGGAALIJEEH-UHFFFAOYSA-N 0.000 description 1
BLHOZSODXSCQQE-UHFFFAOYSA-N benzyl n-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-1-piperidin-1-ylpropan-2-yl]carbamate Chemical compound C1CCCCN1C(=O)C(CNC(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 BLHOZSODXSCQQE-UHFFFAOYSA-N 0.000 description 1
VEVJEGXFKLTFGU-UHFFFAOYSA-N benzyl n-[3-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-1-oxo-1-piperidin-1-ylpropan-2-yl]carbamate Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCC(C(=O)N1CCCCC1)NC(=O)OCC1=CC=CC=C1 VEVJEGXFKLTFGU-UHFFFAOYSA-N 0.000 description 1
239000012472 biological sample Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
CWBHKBKGKCDGDM-UHFFFAOYSA-N bis[(2,2,2-trifluoroacetyl)oxy]boranyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OB(OC(=O)C(F)(F)F)OC(=O)C(F)(F)F CWBHKBKGKCDGDM-UHFFFAOYSA-N 0.000 description 1
208000015294 blood coagulation disease Diseases 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
239000003593 chromogenic compound Substances 0.000 description 1
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
230000035602 clotting Effects 0.000 description 1
230000009852 coagulant defect Effects 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
239000013068 control sample Substances 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229940045803 cuprous chloride Drugs 0.000 description 1
MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
CGJNXSWIIBSXII-UHFFFAOYSA-N dibenzofuran-3-sulfonyl chloride Chemical compound C1=CC=C2C3=CC=C(S(=O)(=O)Cl)C=C3OC2=C1 CGJNXSWIIBSXII-UHFFFAOYSA-N 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 1
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 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
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
AFEGCPOYOQKHES-UHFFFAOYSA-N ethyl 1-benzyl-4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(C(=O)C2CCN(CC2)C=2C=CN=CC=2)CCN1CC1=CC=CC=C1 AFEGCPOYOQKHES-UHFFFAOYSA-N 0.000 description 1
NWVNCURBYFGBFL-UHFFFAOYSA-N ethyl 1-naphthalen-2-ylsulfonylpiperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 NWVNCURBYFGBFL-UHFFFAOYSA-N 0.000 description 1
QKXPWHLIQGFVNZ-UHFFFAOYSA-N ethyl 1-naphthalen-2-ylsulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 QKXPWHLIQGFVNZ-UHFFFAOYSA-N 0.000 description 1
PTFXZNOFHNRSLV-UHFFFAOYSA-N ethyl 1-pyrimidin-4-ylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC=NC=N1 PTFXZNOFHNRSLV-UHFFFAOYSA-N 0.000 description 1
ZKKOLEGJTTYPDH-UHFFFAOYSA-N ethyl 2-(1-benzylpiperidin-4-ylidene)acetate Chemical compound C1CC(=CC(=O)OCC)CCN1CC1=CC=CC=C1 ZKKOLEGJTTYPDH-UHFFFAOYSA-N 0.000 description 1
AYEMHTUOMNWFPF-UHFFFAOYSA-N ethyl 2-(phenylmethoxycarbonylamino)-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propanoate Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)OCC)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 AYEMHTUOMNWFPF-UHFFFAOYSA-N 0.000 description 1
MQTCQNBIJOCDKF-SFHVURJKSA-N ethyl 2-[[(2s)-2-amino-3-phenylpropanoyl]-benzylamino]acetate Chemical compound O=C([C@@H](N)CC=1C=CC=CC=1)N(CC(=O)OCC)CC1=CC=CC=C1 MQTCQNBIJOCDKF-SFHVURJKSA-N 0.000 description 1
IHSUFLCKRIHFGY-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate Chemical compound CCOC(=O)CC1CCNCC1 IHSUFLCKRIHFGY-UHFFFAOYSA-N 0.000 description 1
NWDOKKKZFXSKBT-UHFFFAOYSA-N ethyl 4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound C1CNC(C(=O)OCC)CN1C(=O)C1CCN(C=2C=CN=CC=2)CC1 NWDOKKKZFXSKBT-UHFFFAOYSA-N 0.000 description 1
DKBLHTZJXOZZBP-UHFFFAOYSA-N ethyl 4-[4-[4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazin-1-yl]sulfonylphenyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=C(S(=O)(=O)N2CCN(CC2)C(=O)C2CCN(CC2)C=2C=CN=CC=2)C=C1 DKBLHTZJXOZZBP-UHFFFAOYSA-N 0.000 description 1
YCBJOQUNPLTBGG-UHFFFAOYSA-N ethyl 4-iodobenzoate Chemical compound CCOC(=O)C1=CC=C(I)C=C1 YCBJOQUNPLTBGG-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
239000003527 fibrinolytic agent Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
210000003709 heart valve Anatomy 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000012623 in vivo measurement Methods 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
201000004332 intermediate coronary syndrome Diseases 0.000 description 1
201000010849 intracranial embolism Diseases 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
208000028867 ischemia Diseases 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
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
239000008263 liquid aerosol Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 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
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
VJORLHQUWGHZTB-UHFFFAOYSA-N methyl 1-(6-chloronaphthalen-2-yl)sulfonylpiperazine-2-carboxylate Chemical compound COC(=O)C1CNCCN1S(=O)(=O)C1=CC=C(C=C(Cl)C=C2)C2=C1 VJORLHQUWGHZTB-UHFFFAOYSA-N 0.000 description 1
SQXCAHIDKZNQFO-UHFFFAOYSA-N methyl 1-benzylpiperazine-2-carboxylate Chemical compound COC(=O)C1CNCCN1CC1=CC=CC=C1 SQXCAHIDKZNQFO-UHFFFAOYSA-N 0.000 description 1
YHEMYXIJYAOAST-UHFFFAOYSA-N methyl 2-(4-benzylpiperazin-2-yl)acetate Chemical compound C1CNC(CC(=O)OC)CN1CC1=CC=CC=C1 YHEMYXIJYAOAST-UHFFFAOYSA-N 0.000 description 1
PCSXUAYBRBGNBP-UHFFFAOYSA-N methyl 2-[1-naphthalen-2-ylsulfonyl-4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazin-2-yl]acetate Chemical compound C1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C(CC(=O)OC)CN1C(=O)C(CC1)CCN1C1=CC=NC=C1 PCSXUAYBRBGNBP-UHFFFAOYSA-N 0.000 description 1
PNIWMLBJEDJRIE-UHFFFAOYSA-N methyl 2-[[4-(6-bromonaphthalen-2-yl)sulfonyl-1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-2-carbonyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Br)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 PNIWMLBJEDJRIE-UHFFFAOYSA-N 0.000 description 1
JTTKTABRRJIHBA-UHFFFAOYSA-N methyl 4-(6-chloronaphthalen-2-yl)sulfonyl-1-(1-phenylmethoxycarbonylpiperidine-4-carbonyl)piperazine-2-carboxylate Chemical compound COC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C(=O)OCC1=CC=CC=C1 JTTKTABRRJIHBA-UHFFFAOYSA-N 0.000 description 1
MIAHXESCYBTJBS-UHFFFAOYSA-N methyl 4-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]butanoate Chemical compound C1=CC=CC2=CC(S(=O)(=O)NCC(=O)NCCCC(=O)OC)=CC=C21 MIAHXESCYBTJBS-UHFFFAOYSA-N 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
GDEPRGDONNEERN-UHFFFAOYSA-N n-(3-amino-1-oxo-1-piperidin-1-ylpropan-2-yl)-2-(naphthalen-2-ylsulfonylamino)acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CN)C(=O)N1CCCCC1 GDEPRGDONNEERN-UHFFFAOYSA-N 0.000 description 1
KCNNQVSCOOPIEE-UHFFFAOYSA-N n-(3-amino-1-oxo-1-piperidin-1-ylpropan-2-yl)-2-(naphthalen-2-ylsulfonylamino)acetamide;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CN)C(=O)N1CCCCC1 KCNNQVSCOOPIEE-UHFFFAOYSA-N 0.000 description 1
PEIYLHSJJJVHFH-MHZLTWQESA-N n-[(2s)-1,4-dioxo-1-piperidin-1-yl-4-(4-pyridin-4-ylpiperazin-1-yl)butan-2-yl]-2-(naphthalen-2-ylsulfonylamino)acetamide Chemical compound C([C@H](NC(CNS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)=O)C(=O)N1CCCCC1)C(=O)N(CC1)CCN1C1=CC=NC=C1 PEIYLHSJJJVHFH-MHZLTWQESA-N 0.000 description 1
ROFYUOJJHNNMFT-SANMLTNESA-N n-[(2s)-1,4-dioxo-1-piperidin-1-yl-4-(4-pyridin-4-ylpiperazin-1-yl)butan-2-yl]naphthalene-2-sulfonamide Chemical compound O=C([C@@H](NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC(=O)N1CCN(CC1)C=1C=CN=CC=1)N1CCCCC1 ROFYUOJJHNNMFT-SANMLTNESA-N 0.000 description 1
OPMXMZPUDFMNPT-UHFFFAOYSA-N n-[1-(1-pyridin-4-ylpiperidine-4-carbonyl)piperidin-4-yl]naphthalene-2-sulfonamide Chemical compound C1CC(NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C(CC1)CCN1C1=CC=NC=C1 OPMXMZPUDFMNPT-UHFFFAOYSA-N 0.000 description 1
GBPTUIOTIOGRAG-UHFFFAOYSA-N n-[2-(naphthalen-2-ylsulfonylamino)-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1CN(C=2C=CN=CC=2)CCC1C(=O)NCC(NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)C(=O)N1CCCCC1 GBPTUIOTIOGRAG-UHFFFAOYSA-N 0.000 description 1
QNKPXSKZISXBKI-UHFFFAOYSA-N n-[2-(naphthalene-2-carbonylamino)-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1CN(C=2C=CN=CC=2)CCC1C(=O)NCC(NC(=O)C=1C=C2C=CC=CC2=CC=1)C(=O)N1CCCCC1 QNKPXSKZISXBKI-UHFFFAOYSA-N 0.000 description 1
VOLAJACORBQGLG-UHFFFAOYSA-N n-[2-[(4-methylphenyl)carbamoylamino]-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1=CC(C)=CC=C1NC(=O)NC(C(=O)N1CCCCC1)CNC(=O)C1CCN(C=2C=CN=CC=2)CC1 VOLAJACORBQGLG-UHFFFAOYSA-N 0.000 description 1
NNEOQCFERAOUHH-UHFFFAOYSA-N n-[2-[3-(naphthalen-2-ylsulfonylamino)propanoylamino]-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 NNEOQCFERAOUHH-UHFFFAOYSA-N 0.000 description 1
REYZEFJQKBFDRA-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxo-3-piperidin-1-ylpropyl]-4-pyridin-4-ylpiperazine-1-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)N(CC1)CCN1C1=CC=NC=C1 REYZEFJQKBFDRA-UHFFFAOYSA-N 0.000 description 1
PANXALZQXVUDFT-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCCNC(=O)C(CC1)CCN1C1=CC=NC=C1 PANXALZQXVUDFT-UHFFFAOYSA-N 0.000 description 1
PDCFTAZCJQZPNN-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethyl]-4-pyridin-4-ylpiperazine-1-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCCNC(=O)N(CC1)CCN1C1=CC=NC=C1 PDCFTAZCJQZPNN-UHFFFAOYSA-N 0.000 description 1
GKCXZRRASPATBZ-UHFFFAOYSA-N n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethyl]piperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NCCNC(=O)C1CCNCC1 GKCXZRRASPATBZ-UHFFFAOYSA-N 0.000 description 1
IKYQMGVEICKMKU-UHFFFAOYSA-N n-[2-[[2-[(3,4-dichlorophenyl)sulfonylamino]acetyl]amino]-3-oxo-3-piperidin-1-ylpropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1=C(Cl)C(Cl)=CC=C1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CNC(=O)C1CCN(C=2C=CN=CC=2)CC1 IKYQMGVEICKMKU-UHFFFAOYSA-N 0.000 description 1
BLZLGCIWYOVCGJ-UHFFFAOYSA-N n-[2-oxo-2-(4-pyridin-4-ylpiperazin-1-yl)ethyl]naphthalene-2-sulfonamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)N(CC1)CCN1C1=CC=NC=C1 BLZLGCIWYOVCGJ-UHFFFAOYSA-N 0.000 description 1
CWRPRKRVGYVGBZ-UHFFFAOYSA-N n-[3-(4-methylpiperidin-1-yl)-2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxopropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C1CC(C)CCN1C(=O)C(NC(=O)CNS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CNC(=O)C1CCN(C=2C=CN=CC=2)CC1 CWRPRKRVGYVGBZ-UHFFFAOYSA-N 0.000 description 1
CXGHHBNINQZWNO-UHFFFAOYSA-N n-[3-(naphthalen-2-ylsulfonylamino)propyl]-2-(4-pyridin-4-ylpiperazin-1-yl)acetamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCCCNC(=O)CN(CC1)CCN1C1=CC=NC=C1 CXGHHBNINQZWNO-UHFFFAOYSA-N 0.000 description 1
UMQDUHGVZJWEQN-UHFFFAOYSA-N n-[3-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-4-oxo-4-piperidin-1-ylbutyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCCCC1)CCNC(=O)C(CC1)CCN1C1=CC=NC=C1 UMQDUHGVZJWEQN-UHFFFAOYSA-N 0.000 description 1
PDCGLBRUEFMHMN-UHFFFAOYSA-N n-[3-morpholin-4-yl-2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxopropyl]-1-pyridin-4-ylpiperidine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(C(=O)N1CCOCC1)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 PDCGLBRUEFMHMN-UHFFFAOYSA-N 0.000 description 1
MHUDVHMZBINMRO-UHFFFAOYSA-N n-[4-oxo-4-(4-pyridin-4-ylpiperazin-1-yl)butyl]naphthalene-2-sulfonamide Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCCCC(=O)N(CC1)CCN1C1=CC=NC=C1 MHUDVHMZBINMRO-UHFFFAOYSA-N 0.000 description 1
DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
XNLBCXGRQWUJLU-UHFFFAOYSA-N naphthalene-2-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CC=C21 XNLBCXGRQWUJLU-UHFFFAOYSA-N 0.000 description 1
SWBLLSQMOMPTMC-UHFFFAOYSA-N naphthalene-2-sulfonamide Chemical compound C1=CC=CC2=CC(S(=O)(=O)N)=CC=C21 SWBLLSQMOMPTMC-UHFFFAOYSA-N 0.000 description 1
150000002790 naphthalenes Chemical class 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
SIRSTRHGFGFVME-UHFFFAOYSA-N piperazin-2-ylmethanol Chemical compound OCC1CNCCN1 SIRSTRHGFGFVME-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
XCOWFHRNGJAHDO-UHFFFAOYSA-N piperidin-4-yl acetate Chemical compound CC(=O)OC1CCNCC1 XCOWFHRNGJAHDO-UHFFFAOYSA-N 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000000106 platelet aggregation inhibitor Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
ZPWQALCOMQRMRK-UHFFFAOYSA-M sodium;6-hydroxynaphthalene-2-sulfonate Chemical compound [Na+].C1=C(S([O-])(=O)=O)C=CC2=CC(O)=CC=C21 ZPWQALCOMQRMRK-UHFFFAOYSA-M 0.000 description 1
KATWGOIXXDLFBD-UHFFFAOYSA-M sodium;6-methoxynaphthalene-2-sulfonate Chemical compound [Na+].C1=C(S([O-])(=O)=O)C=CC2=CC(OC)=CC=C21 KATWGOIXXDLFBD-UHFFFAOYSA-M 0.000 description 1
IVXSQYUPCUOMRV-UHFFFAOYSA-M sodium;7-sulfonaphthalen-2-olate Chemical compound [Na+].C1=CC(S([O-])(=O)=O)=CC2=CC(O)=CC=C21 IVXSQYUPCUOMRV-UHFFFAOYSA-M 0.000 description 1
QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000012306 spectroscopic technique Methods 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
150000003440 styrenes Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
WQKATDBRQRNLIM-UHFFFAOYSA-N tert-butyl 2-(4-pyridin-4-ylpiperazin-1-yl)acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCN1C1=CC=NC=C1 WQKATDBRQRNLIM-UHFFFAOYSA-N 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
AQXUBBRRKJFPFB-UHFFFAOYSA-N tert-butyl 4-(1-pyridin-4-ylpiperidine-4-carbonyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)C1CCN(C=2C=CN=CC=2)CC1 AQXUBBRRKJFPFB-UHFFFAOYSA-N 0.000 description 1
MLYLEMNFKQDIPE-UHFFFAOYSA-N tert-butyl 4-(4-pyridin-4-ylpiperazine-1-carbonyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)N1CCN(C=2C=CN=CC=2)CC1 MLYLEMNFKQDIPE-UHFFFAOYSA-N 0.000 description 1
BROXTLPJTCIVFV-UHFFFAOYSA-N tert-butyl 4-(naphthalen-2-ylmethyl)-3-oxopiperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=C(C=CC=C2)C2=C1 BROXTLPJTCIVFV-UHFFFAOYSA-N 0.000 description 1
NQOCULMDVDQMOS-UHFFFAOYSA-N tert-butyl 4-[2-(4-pyridin-4-ylpiperazin-1-yl)acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)CN1CCN(C=2C=CN=CC=2)CC1 NQOCULMDVDQMOS-UHFFFAOYSA-N 0.000 description 1
UCEPOFMOGYJFNX-UHFFFAOYSA-N tert-butyl 4-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]ethylcarbamoyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)NCCNC(=O)CNS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 UCEPOFMOGYJFNX-UHFFFAOYSA-N 0.000 description 1
PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
JFVULKKBDOWQMY-UHFFFAOYSA-N tert-butyl 4-naphthalen-2-ylsulfanylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1SC1=CC=C(C=CC=C2)C2=C1 JFVULKKBDOWQMY-UHFFFAOYSA-N 0.000 description 1
RWTNFADRHNFHGI-UHFFFAOYSA-N tert-butyl 4-naphthalen-2-ylsulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 RWTNFADRHNFHGI-UHFFFAOYSA-N 0.000 description 1
GBDVQECHBDGGAF-UHFFFAOYSA-N tert-butyl 4-naphthalen-2-ylsulfonylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 GBDVQECHBDGGAF-UHFFFAOYSA-N 0.000 description 1
FVWRGJAGTFCEBY-UHFFFAOYSA-N tert-butyl n-(2-amino-3-oxo-3-piperidin-1-ylpropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(N)C(=O)N1CCCCC1 FVWRGJAGTFCEBY-UHFFFAOYSA-N 0.000 description 1
AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
HJPOCYREPQSZTC-UHFFFAOYSA-N tert-butyl n-[1-phenyl-3-[(1-pyridin-4-ylpiperidine-4-carbonyl)amino]propan-2-yl]carbamate Chemical compound C=1C=CC=CC=1CC(NC(=O)OC(C)(C)C)CNC(=O)C(CC1)CCN1C1=CC=NC=C1 HJPOCYREPQSZTC-UHFFFAOYSA-N 0.000 description 1
YQYYSHMQJAMBQY-UHFFFAOYSA-N tert-butyl n-[2-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-3-oxo-3-piperidin-1-ylpropyl]carbamate Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CNC(=O)OC(C)(C)C)C(=O)N1CCCCC1 YQYYSHMQJAMBQY-UHFFFAOYSA-N 0.000 description 1
LJXQFOLCPZTOPH-UHFFFAOYSA-N tert-butyl n-[3-[[2-(naphthalen-2-ylsulfonylamino)acetyl]amino]-4-oxo-4-piperidin-1-ylbutyl]carbamate Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)NCC(=O)NC(CCNC(=O)OC(C)(C)C)C(=O)N1CCCCC1 LJXQFOLCPZTOPH-UHFFFAOYSA-N 0.000 description 1
DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229960003766 thrombin (human) Drugs 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
230000001732 thrombotic effect Effects 0.000 description 1
239000002396 thromboxane receptor blocking agent Substances 0.000 description 1
239000003768 thromboxane synthase inhibitor Substances 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
229960000187 tissue plasminogen activator Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000001631 vena cava inferior Anatomy 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Hematology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Materials For Medical Uses (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)
Pyridine Compounds (AREA)
Cephalosporin Compounds (AREA)

NO971415A 1994-09-26 1997-03-25 Aminoheterocykliske derivater som anti-trombose- eller antikoagulantmidler NO971415L (no)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB9419341A GB9419341D0 (en)	1994-09-26	1994-09-26	Aminoheterocyclic derivatives
GBGB9425789.6A GB9425789D0 (en)	1994-12-21	1994-12-21	Aminoheterocyclic derivatives
GBGB9511051.6A GB9511051D0 (en)	1995-06-01	1995-06-01	Aminoheterocyclic derivatives
PCT/GB1995/002285 WO1996010022A1 (en)	1994-09-26	1995-09-25	Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents

Publications (2)

Publication Number	Publication Date
NO971415D0 NO971415D0 (no)	1997-03-25
NO971415L true NO971415L (no)	1997-05-22

Family

ID=27267394

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO971415A NO971415L (no)	1994-09-26	1997-03-25	Aminoheterocykliske derivater som anti-trombose- eller antikoagulantmidler

Country Status (18)

Country	Link
US (3)	US5965559A (de)
EP (1)	EP0783500B1 (de)
JP (1)	JPH10506122A (de)
AT (1)	ATE168685T1 (de)
AU (1)	AU696491B2 (de)
BR (1)	BR9509045A (de)
CA (1)	CA2197471A1 (de)
CZ (1)	CZ285370B6 (de)
DE (1)	DE69503647T2 (de)
DK (1)	DK0783500T3 (de)
ES (1)	ES2119472T3 (de)
HU (1)	HUT77769A (de)
IL (1)	IL115420A0 (de)
NO (1)	NO971415L (de)
NZ (1)	NZ292983A (de)
PL (1)	PL319430A1 (de)
SK (1)	SK38597A3 (de)
WO (1)	WO1996010022A1 (de)

Families Citing this family (115)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL115420A0 (en)	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
EE9700141A (et) *	1994-12-23	1997-12-15	Dr. Karl Thomae Gmbh	Piperasiinderivaadid, neid sisaldavad ravimid, nende kasutamine ja valmistamise meetod
EP0813525B9 (de)	1995-03-10	2004-02-04	Berlex Laboratories, Inc.	Benzamidin-derivate, deren herstellung und deren verwendung als anti-koagulantien
GB9516709D0 (en) *	1995-08-15	1995-10-18	Zeneca Ltd	Medicament
GB9602166D0 (en) *	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
US6313127B1 (en)	1996-02-02	2001-11-06	Zeneca Limited	Heterocyclic compounds useful as pharmaceutical agents
GB9602294D0 (en) *	1996-02-05	1996-04-03	Zeneca Ltd	Heterocyclic compounds
US5994375A (en)	1996-02-12	1999-11-30	Berlex Laboratories, Inc.	Benzamidine derivatives substituted by amino acid and hydroxy acid derivatives and their use as anti-coagulants
WO1998006705A1 (en) *	1996-08-14	1998-02-19	Zeneca Limited	Substituted pyrimidine derivatives and their pharmaceutical use
US5693641A (en) *	1996-08-16	1997-12-02	Berlex Laboratories Inc.	Bicyclic pyrimidine derivatives and their use as anti-coagulants
US5753635A (en) *	1996-08-16	1998-05-19	Berlex Laboratories, Inc.	Purine derivatives and their use as anti-coagulants
US6008234A (en) *	1996-09-12	1999-12-28	Berlex Laboratories, Inc.	Benzamidine derivatives substituted by cyclic amino acid and cyclic hydroxy acid derivatives and their use as anti-coagulants
CA2264521A1 (en)	1996-09-12	1998-03-19	Schering Aktiengesellschaft	Benzamidine derivatives substituted by cyclic amino acid or cyclic hydroxy acid derivatives and their use as anti-coagulants
US6004985A (en) *	1996-10-09	1999-12-21	Berlex Laboratories, Inc.	Thio acid derived monocylic N-heterocyclics as anticoagulants
UA56197C2 (uk) *	1996-11-08	2003-05-15	Зенека Лімітед	Гетероциклічні похідні
WO1998035956A1 (en) *	1997-02-13	1998-08-20	Zeneca Limited	Heterocyclic compounds useful as oxido-squalene cyclase inhibitors
JP2001511799A (ja) *	1997-02-13	2001-08-14	ゼネカ・リミテッド	オキシド−スクアレンシクラーゼ阻害剤として有用なヘテロ環式化合物
US6359134B1 (en)	1997-05-30	2002-03-19	Takeda Chemical Industries, Ltd.	Sulfonamide derivatives, their production and use
GB9715892D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9715895D0 (en) *	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9715894D0 (en) *	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic derivatives
WO1999016747A1 (en)	1997-09-30	1999-04-08	Daiichi Pharmaceutical Co., Ltd.	Sulfonyl derivatives
US6686364B2 (en)	1997-12-08	2004-02-03	Berlex Laboratories, Inc.	Benzamidine derivatives and their use as anti-coagulants
US6140351A (en) *	1997-12-19	2000-10-31	Berlex Laboratories, Inc.	Ortho-anthranilamide derivatives as anti-coagulants
NZ503809A (en)	1997-12-19	2002-04-26	Schering Ag	Ortho-anthranilamide derivatives as anti-coagulants
AU1692399A (en) *	1997-12-26	1999-07-19	Mochida Pharmaceutical Co., Ltd.	Aromatic compounds having cyclic amino or salts thereof
YU47600A (sh)	1998-01-27	2002-09-19	Aventis Pharmaceuticals Products Inc.	SUPSTITUISANI OKSOAZAHETEROCIKLIL INHIBITORI FAKTORA Xa
CN1290254A (zh)	1998-02-05	2001-04-04	武田药品工业株式会社	氨磺酰衍生物及其制备和用途
GB9809349D0 (en)	1998-05-02	1998-07-01	Zeneca Ltd	Heterocyclic derivatives
GB9809351D0 (en) *	1998-05-02	1998-07-01	Zeneca Ltd	Heterocyclic derivatives
CN1133634C (zh)	1998-05-02	2004-01-07	阿斯特拉曾尼卡有限公司	抑制因子Xa的杂环衍生物
DE19835950A1 (de) *	1998-08-08	2000-02-10	Merck Patent Gmbh	Piperazinonderivate
EP1104754A1 (de) *	1998-08-11	2001-06-06	Daiichi Pharmaceutical Co., Ltd.	Sulfonylderivate
DE19839499A1 (de) *	1998-08-29	2000-03-02	Merck Patent Gmbh	2-Oxo-2H-chinolinderivate
US6262088B1 (en)	1998-11-19	2001-07-17	Berlex Laboratories, Inc.	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
US6127376A (en) *	1998-12-04	2000-10-03	Berlex Laboratories, Inc.	Aryl and heterocyclyl substituted pyrimidine derivatives as anti-coagulants
WO2000038683A1 (en)	1998-12-23	2000-07-06	Du Pont Pharmaceuticals Company	THROMBIN OR FACTOR Xa INHIBITORS
ATE261941T1 (de)	1998-12-24	2004-04-15	Lilly Co Eli	Heterocyclische amide als inhibitoren von faktor xa
GB9902989D0 (en)	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives
ATE325114T1 (de)	1999-06-22	2006-06-15	Takeda Pharmaceutical	Acylhydrazinderivate, verfahren zu ihrer herstellung und ihre verwendung
US6350761B1 (en)	1999-07-30	2002-02-26	Berlex Laboratories, Inc.	Benzenamine derivatives as anti-coagulants
TWI288745B (en)	2000-04-05	2007-10-21	Daiichi Seiyaku Co	Ethylenediamine derivatives
EP1302462A4 (de) *	2000-07-17	2007-07-18	Takeda Pharmaceutical	Sulfonderivate, verfahren zu ihrer herstellung und ihre verwendung
DE10035144A1 (de) *	2000-07-19	2002-01-31	Merck Patent Gmbh	Cyclische Aminosäurederivate
ATE374765T1 (de)	2000-07-27	2007-10-15	Lilly Co Eli	Substituierte heterocyclische amide
AU2001288819A1 (en)	2000-09-11	2002-03-26	Genentech, Inc.	Amidine inhibitors of serine proteases
US6538017B2 (en)	2001-03-09	2003-03-25	Ortho-Mcneil Pharmaceutical, Inc.	Aminopyrrolidine sulfonamides as serine protease inhibitors
US6710061B2 (en)	2001-03-09	2004-03-23	Ortho-Mcneil Pharamceutical, Inc.	Aminopyrrolidine sulfonamides as serine protease inhibitors
WO2002074762A1 (en) *	2001-03-15	2002-09-26	Takeda Chemical Industries, Ltd.	Process for producing sulfone derivative
DE10112768A1 (de) *	2001-03-16	2002-09-19	Merck Patent Gmbh	Phenylderivate 3
KR100863113B1 (ko)	2001-06-20	2008-10-13	다이이찌 산쿄 가부시키가이샤	디아민 유도체
WO2003000657A1 (en)	2001-06-20	2003-01-03	Daiichi Pharmaceutical Co., Ltd.	Diamine derivatives
DE10139060A1 (de)	2001-08-08	2003-02-20	Merck Patent Gmbh	Phenylderivate
DE10247226A1 (de) *	2002-10-10	2004-04-22	Merck Patent Gmbh	Heterocyclische Amide
WO2004035579A1 (ja) *	2002-10-15	2004-04-29	Takeda Pharmaceutical Company Limited	イミダゾピリジン誘導体、その製造法および用途
US20070004736A1 (en) *	2002-11-22	2007-01-04	Keiji Kubo	Imidazole derivative, process for producing the same, and use
CN100513398C (zh)	2002-12-03	2009-07-15	Axys药物公司	作为因子viia抑制剂的2-(2-羟基联苯-3-基)-1h-苯并咪唑-5-甲脒衍生物
DE10302500A1 (de)	2003-01-23	2004-07-29	Merck Patent Gmbh	Carbonsäureamidderivate
DE10308907A1 (de)	2003-02-28	2004-09-09	Merck Patent Gmbh	Ethynylderivate
WO2004087700A1 (fr) *	2003-03-25	2004-10-14	Laboratoires Fournier S.A.	Derives du benzenesulfonamide, leur procede de preparation et leur utilisation de la douleur
HRP20080541T3 (en)	2003-04-23	2008-12-31	Glaxo Group Limited	Piperazine derivatives and their use for the treatment of neurological and psychiatric diseases
JP2007500221A (ja)	2003-05-20	2007-01-11	ジェネンテック・インコーポレーテッド	第ＶＩＩａ因子のベンゾフラン阻害剤
AU2004249670A1 (en)	2003-05-20	2004-12-29	Genentech, Inc.	Acylsulfamide inhibitors of factor VIIa
DE10342108A1 (de)	2003-09-11	2005-04-14	Curacyte Chemistry Gmbh	Basisch-substituierte Benzylaminanaloga als Inhibitoren des Gerinnungsfaktors Xa, ihre Herstellung und Verwendung
US20050119266A1 (en) *	2003-10-01	2005-06-02	Yan Shi	Pyrrolidine and piperidine derivatives as factor Xa inhibitors
DE10358539A1 (de)	2003-12-15	2005-07-07	Merck Patent Gmbh	Carbonsäureamidderivate
TWI396686B (zh) *	2004-05-21	2013-05-21	Takeda Pharmaceutical	環狀醯胺衍生物、以及其製品和用法
MXPA06014573A (es) *	2004-06-24	2007-03-12	Incyte Corp	Compuestos amido y su uso como farmaceuticos.
WO2006004793A2 (en) *	2004-06-28	2006-01-12	Janssen Pharmaceutica Nv	Hetero isonipecotic modulators of vanilloid vr1 receptor
TW200630337A (en)	2004-10-14	2006-09-01	Euro Celtique Sa	Piperidinyl compounds and the use thereof
US20080214495A1 (en) *	2005-07-08	2008-09-04	Astrazeneca Ab	Heterocyclic Sulfonamide Derivatives as Inhibitors of Factor Xa
WO2007008146A1 (en) *	2005-07-08	2007-01-18	Astrazeneca Ab	Heterocyclic sulfonamide derivatives as inhibitors of factor xa
WO2007016496A2 (en) *	2005-08-02	2007-02-08	Neurogen Corporation	Dipiperazinyl ketones and related analogues
WO2007101270A1 (en) *	2006-03-02	2007-09-07	Incyte Corporation	MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME
WO2007110449A1 (en) *	2006-03-29	2007-10-04	Euro-Celtique S.A.	Benzenesulfonamide compounds and their use
WO2007118853A1 (en)	2006-04-13	2007-10-25	Euro-Celtique S.A.	Benzenesulfonamide compounds and their use as blockers of calcium channels
TW200812963A (en) *	2006-04-13	2008-03-16	Euro Celtique Sa	Benzenesulfonamide compounds and the use thereof
AU2007281911B2 (en) *	2006-08-04	2014-02-06	Beth Israel Deaconess Medical Center	Inhibitors of pyruvate kinase and methods of treating disease
DE102006039003A1 (de)	2006-08-19	2008-02-21	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue Verbindungen
WO2008124118A1 (en) *	2007-04-09	2008-10-16	Purdue Pharma L.P.	Benzenesulfonyl compounds and the use therof
KR101171507B1 (ko) *	2007-08-13	2012-08-07	에프. 호프만-라 로슈 아게	신규 피페라진 아마이드 유도체
EP2188269B1 (de)	2007-08-14	2014-05-07	Boehringer Ingelheim International GmbH	Arylsulfonamide mit analgetischer wirkung
EP2025675A1 (de)	2007-08-14	2009-02-18	Boehringer Ingelheim International GmbH	Arylsulfonamide mit analgetischer Wirkung
WO2009040659A2 (en) *	2007-09-28	2009-04-02	Purdue Pharma L.P.	Benzenesulfonamide compounds and the use thereof
CN102985557B (zh)	2009-03-13	2018-06-15	安吉奥斯医药品有限公司	用于细胞增殖相关病症的方法和组合物
JP5756457B2 (ja)	2009-04-06	2015-07-29	アジオスファーマシューティカルズ，インコーポレイテッド	ピルビン酸キナーゼｍ２調節剤、治療組成物および関連する使用方法
PE20120693A1 (es) *	2009-06-29	2012-07-04	Agios Pharmaceuticals Inc	Compuestos heterociclos como moduladores de la piruvato cinasa m2 (pkm2)
DK2448581T3 (en)	2009-06-29	2017-03-13	Agios Pharmaceuticals Inc	Therapeutic compositions and methods for their applications
WO2011050210A1 (en)	2009-10-21	2011-04-28	Agios Pharmaceuticals, Inc.	Methods and compositions for cell-proliferation-related disorders
US9221792B2 (en)	2010-12-17	2015-12-29	Agios Pharmaceuticals, Inc	N-(4-(azetidine-1-carbonyl) phenyl)-(hetero-) arylsulfonamide derivatives as pyruvate kinase M2 (PMK2) modulators
WO2012088314A1 (en)	2010-12-21	2012-06-28	Agios Pharmaceuticals, Inc.	Bicyclic pkm2 activators
TWI549947B (zh)	2010-12-29	2016-09-21	阿吉歐斯製藥公司	治療化合物及組成物
EP2704720B1 (de)	2011-05-03	2019-08-07	Agios Pharmaceuticals, Inc.	Pyruvate kinase r aktivatoren zur verwendung in therapie
PT3406251T (pt)	2011-05-03	2024-01-24	Agios Pharmaceuticals Inc	Ativadores da piruvato-cinase para utilização em terapia
CN102827170A (zh)	2011-06-17	2012-12-19	安吉奥斯医药品有限公司	治疗活性组合物和它们的使用方法
CN102827073A (zh)	2011-06-17	2012-12-19	安吉奥斯医药品有限公司	治疗活性组合物和它们的使用方法
RS54738B1 (sr) *	2011-11-29	2016-10-31	Perosphere Inc	Agensi koji vrše reverziju antikoagulanta
SMT201800334T1 (it)	2012-01-06	2018-09-13	Agios Pharmaceuticals Inc	Composti terapeuticamente attivi e loro metodi di utilizzo
US9474779B2 (en)	2012-01-19	2016-10-25	Agios Pharmaceuticals, Inc.	Therapeutically active compositions and their methods of use
US20130303509A1 (en)	2012-05-11	2013-11-14	Abbvie Inc.	Nampt inhibitors
WO2014062511A1 (en)	2012-10-15	2014-04-24	Agios Pharmaceuticals, Inc.	Therapeutic compounds and compositions
CN105593215B (zh)	2013-07-11	2019-01-15	安吉奥斯医药品有限公司	用于治疗癌症的作为idh2突变体抑制剂的2,4-或4,6-二氨基嘧啶化合物
WO2015003355A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
WO2015003360A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
WO2015010297A1 (en)	2013-07-25	2015-01-29	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
PH12021551647A1 (en)	2014-03-14	2022-06-06	Agios Pharmaceuticals Inc	Pharmaceutical compositions of therapeutically active compounds
MX384883B (es)	2015-06-11	2025-03-14	Agios Pharmaceuticals Inc	Métodos para usar activadores de piruvato cinasa.
HUE067449T2 (hu)	2015-10-15	2024-10-28	Servier Lab	Ivozidenib, citarabin és daunorubicin vagy idarubicin kombinációs terápa akut mielogén leukémia kezelésére
MD3362066T2 (ro)	2015-10-15	2022-08-31	Les Laboratoires Servier Sas	Terapie combinată pentru tratamentul tumorilor maligne
EP3774722B1 (de) *	2018-04-04	2024-07-24	Epiodyne, Inc.	Opioid-rezeptor-modulatoren sowie zugehörige produkte und verfahren
US10980788B2 (en)	2018-06-08	2021-04-20	Agios Pharmaceuticals, Inc.	Therapy for treating malignancies
DK3993876T3 (en)	2019-07-01	2024-12-02	Tonix Pharma Ltd	Anti-cd154 antibodies and uses thereof
GB202010626D0 (en)	2020-07-10	2020-08-26	Univ Nottingham	Compound
AU2022205313A1 (en)	2021-01-06	2023-07-20	Tonix Pharma Limited	Methods of inducing immune tolerance with modified anti-cd154 antibodies
WO2025248134A1 (en)	2024-05-31	2025-12-04	Tonix Pharma Limited	Treatment methods comprising administration of modified cd154 antibodies

Family Cites Families (66)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AT340933B (de)	1973-08-20	1978-01-10	Thomae Gmbh Dr K	Verfahren zur herstellung neuer pyrimidinderivate und ihrer saureadditionssalze
US4167567A (en) *	1978-05-05	1979-09-11	The Upjohn Company	Antihypertensive 4-aminoquinolines
US4231938A (en)	1979-06-15	1980-11-04	Merck & Co., Inc.	Hypocholesteremic fermentation products and process of preparation
SE8203887D0 (sv)	1982-06-23	1982-06-23	Kabivitrum Ab	Nya trombininhiberande foreningar
DE3246932A1 (de)	1982-12-16	1984-06-20	Schering AG, 1000 Berlin und 4709 Bergkamen	Substituierte 5h-pyrimido(5,4-b)indole
US4560610A (en)	1983-04-05	1985-12-24	Dayco Corporation	Polymeric-coated fabric layer
FR2557570B1 (fr)	1984-01-04	1986-04-18	Adir	Nouveaux derives de la quinoleine, leur procede de preparation et les compositions pharmaceutiques les renfermant
US4840963A (en)	1984-03-14	1989-06-20	Merck & Co., Inc.	2-Sulfamoyl-1H-indole derivatives for the treatment of elevated intraocular pressure
GB8601160D0 (en)	1986-01-17	1986-02-19	Fujisawa Pharmaceutical Co	Heterocyclic compounds
GB8603120D0 (en) *	1986-02-07	1986-03-12	Pfizer Ltd	Anti-dysrhythmia agents
GB8609630D0 (en)	1986-04-19	1986-05-21	Pfizer Ltd	Anti-arrhythmia agents
GB8710494D0 (en)	1987-05-02	1987-06-03	Pfizer Ltd	Antiarrhythmic agents
JPH0696575B2 (ja) *	1987-09-17	1994-11-30	三菱化成株式会社	４−アミノピリジン誘導体及びその酸付加塩
US4871721A (en)	1988-01-11	1989-10-03	E. R. Squibb & Sons, Inc.	Phosphorus-containing squalene synthetase inhibitors
GB8817315D0 (en)	1988-07-20	1988-08-24	Pfizer Ltd	Triazole antifungal agents
GB8819307D0 (en)	1988-08-13	1988-09-14	Pfizer Ltd	Antiarrhythmic agents
DE3905364A1 (de)	1989-02-22	1990-08-23	Hoechst Ag	Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als tool
GB8905526D0 (en)	1989-03-10	1989-04-19	Fujisawa Pharmaceutical Co	N-containing heterocyclic compounds,processes for the preparation thereof and composition comprising the same
IE64358B1 (en)	1989-07-18	1995-07-26	Ici Plc	Diaryl ether heterocycles
US5032604A (en)	1989-12-08	1991-07-16	Merck & Co., Inc.	Class III antiarrhythmic agents
DE3943225A1 (de)	1989-12-23	1991-06-27	Schering Ag	Neue ss-carboline, verfahren zu deren herstellung und deren verwendung in arzneimitteln
KR920703558A (ko)	1990-11-15	1992-12-18	원본미기재	메타-치환 페닐알라닌 유도체
EP0495750A3 (en) *	1991-01-14	1992-09-16	Ciba-Geigy Ag	Heterocyclic hydroxylamine
IT1245712B (it) *	1991-04-09	1994-10-14	Boehringer Mannheim Italia	Ammine eterocicliche utili terapia dell'asma e dell'infiammazione delle vie aeree
FR2676054B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
EP0589985A1 (de) *	1991-06-21	1994-04-06	Boehringer Mannheim Italia S.P.A.	2-amino-4-aryl-thiazole-derivate mit asthma-hemmender und entzündungshemmender wirkung auf der atemwegen
EP0604529A1 (de)	1991-09-19	1994-07-06	Smithkline Beecham Corporation	Pyridinverbindungen für die Behandlung von Leukotrien-verwandten Krankheiten
US5541330A (en)	1991-12-10	1996-07-30	Eastman Kodak Company	Ion-sensitive compounds
PH31294A (en)	1992-02-13	1998-07-06	Thomae Gmbh Dr K	Benzimidazolyl derivatives, pharmaceutical compositions containing these compounds and process for preparing them.
HU211995B (en) *	1992-06-30	1996-01-29	Gyogyszerkutato Intezet	Process to prepare novel benzoyl amino acid derivs. and pharmaceutical compns. contg.them
US5371091A (en) *	1992-08-31	1994-12-06	Bristol-Myers Squibb Company	Heteroaromatic amine thrombin inhibitors
FR2697252B1 (fr)	1992-10-28	1994-12-09	Fournier Ind & Sante	Dérivés de 1,2,3,5,6,7,8,8a-octahydro-5,5,8a-triméthyl-(8abeta)-6-isoquinolineamine, leur procédé de préparation et leur utilisation en thérapeutique.
DE4243858A1 (de) *	1992-12-23	1994-06-30	Thomae Gmbh Dr K	Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
US5332822A (en) *	1992-12-24	1994-07-26	Bristol-Myers Squibb Company	Heteroaromatic and thioheteroaromatic substituted sulfonamide thrombin inhibitors
US5364865A (en)	1992-12-30	1994-11-15	Sterling Winthrop Inc.	Phenoxy- and phenoxyalkyl-piperidines as antiviral agents
DE4302485A1 (de)	1993-01-29	1994-08-04	Merck Patent Gmbh	Piperazinderivate
WO1994018185A1 (de)	1993-02-10	1994-08-18	Pentapharm Ag	Piperazide von substituierten phenylalanin-derivativen als thrombin inhibitoren
TW257757B (de) *	1993-03-03	1995-09-21	Boehringer Mannheim Gmbh
DE4306506A1 (de) *	1993-03-03	1994-09-08	Boehringer Mannheim Gmbh	Neue 4-Alkylaminopyridine - Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
DE4306873A1 (de) *	1993-03-05	1994-09-08	Boehringer Mannheim Gmbh	Neue 4-Aminopyridine-Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
EP0690847A1 (de)	1993-03-29	1996-01-10	Zeneca Limited	Heterozyklische derivate als plätchenaggregationsinhibitoren
DK0691959T3 (da)	1993-03-29	1999-04-26	Zeneca Ltd	Heterocykliske derivater som blodpladeaggregations-inhibitorer
US5681954A (en)	1993-05-14	1997-10-28	Daiichi Pharmaceutical Co., Ltd.	Piperazine derivatives
WO1996005189A1 (de)	1994-08-09	1996-02-22	Pentapharm Ag	Neue inhibitoren vom benzamidintyp
IL115420A0 (en)	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
EP0796098A4 (de)	1994-12-22	1998-04-29	Smithkline Beecham Corp	Fibrinogenrezeptor-antagonisten
EP0801650A4 (de)	1994-12-22	1998-05-06	Smithkline Beecham Corp	Fibrinogenrezeptor-antagonisten
IL117149A0 (en)	1995-02-23	1996-06-18	Schering Corp	Muscarinic antagonists
IL117580A0 (en)	1995-03-29	1996-07-23	Merck & Co Inc	Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
US5856326A (en)	1995-03-29	1999-01-05	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
IT1282797B1 (it)	1995-04-21	1998-03-31	Colla Paolo	Pirril-(indolil)-aril-sulfoni e relativo processo di produzione ed impiego nella terapia delle infezioni da virus dell'aids
GB9516709D0 (en)	1995-08-15	1995-10-18	Zeneca Ltd	Medicament
US6313127B1 (en)	1996-02-02	2001-11-06	Zeneca Limited	Heterocyclic compounds useful as pharmaceutical agents
GB9602166D0 (en)	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
GB9602294D0 (en)	1996-02-05	1996-04-03	Zeneca Ltd	Heterocyclic compounds
ES2186874T3 (es)	1996-02-22	2003-05-16	Bristol Myers Squibb Pharma Co	Analogos de m-amidinofenilo como inhibidores del factor xa.
WO1998006705A1 (en)	1996-08-14	1998-02-19	Zeneca Limited	Substituted pyrimidine derivatives and their pharmaceutical use
UA56197C2 (uk)	1996-11-08	2003-05-15	Зенека Лімітед	Гетероциклічні похідні
JP2001511799A (ja)	1997-02-13	2001-08-14	ゼネカ・リミテッド	オキシド−スクアレンシクラーゼ阻害剤として有用なヘテロ環式化合物
WO1998035956A1 (en)	1997-02-13	1998-08-20	Zeneca Limited	Heterocyclic compounds useful as oxido-squalene cyclase inhibitors
GB9715895D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9715892D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9715894D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic derivatives
GB9809349D0 (en)	1998-05-02	1998-07-01	Zeneca Ltd	Heterocyclic derivatives
CN1133634C (zh)	1998-05-02	2004-01-07	阿斯特拉曾尼卡有限公司	抑制因子Xa的杂环衍生物
GB9902989D0 (en)	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives

1995
- 1995-09-24 IL IL11542095A patent/IL115420A0/xx unknown
- 1995-09-25 WO PCT/GB1995/002285 patent/WO1996010022A1/en not_active Ceased
- 1995-09-25 SK SK385-97A patent/SK38597A3/sk unknown
- 1995-09-25 JP JP8511499A patent/JPH10506122A/ja not_active Withdrawn
- 1995-09-25 PL PL95319430A patent/PL319430A1/xx unknown
- 1995-09-25 AU AU35307/95A patent/AU696491B2/en not_active Ceased
- 1995-09-25 CA CA002197471A patent/CA2197471A1/en not_active Abandoned
- 1995-09-25 DK DK95932128T patent/DK0783500T3/da active
- 1995-09-25 EP EP95932128A patent/EP0783500B1/de not_active Expired - Lifetime
- 1995-09-25 DE DE69503647T patent/DE69503647T2/de not_active Expired - Fee Related
- 1995-09-25 AT AT95932128T patent/ATE168685T1/de not_active IP Right Cessation
- 1995-09-25 US US08/817,031 patent/US5965559A/en not_active Expired - Fee Related
- 1995-09-25 HU HU9702052A patent/HUT77769A/hu unknown
- 1995-09-25 ES ES95932128T patent/ES2119472T3/es not_active Expired - Lifetime
- 1995-09-25 CZ CZ97893A patent/CZ285370B6/cs not_active IP Right Cessation
- 1995-09-25 BR BR9509045A patent/BR9509045A/pt not_active Application Discontinuation
- 1995-09-25 NZ NZ292983A patent/NZ292983A/xx unknown
1997
- 1997-03-25 NO NO971415A patent/NO971415L/no unknown
1999
- 1999-08-09 US US09/369,857 patent/US6225309B1/en not_active Expired - Fee Related
2001
- 2001-03-08 US US09/800,745 patent/US6730672B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0783500B1 (de)	1998-07-22
NZ292983A (en)	1998-12-23
US5965559A (en)	1999-10-12
NO971415D0 (no)	1997-03-25
CA2197471A1 (en)	1996-04-04
MX9701841A (es)	1998-10-31
EP0783500A1 (de)	1997-07-16
JPH10506122A (ja)	1998-06-16
US6225309B1 (en)	2001-05-01
SK38597A3 (en)	1997-09-10
CZ285370B6 (cs)	1999-07-14
DE69503647T2 (de)	1999-01-14
US20020119968A1 (en)	2002-08-29
BR9509045A (pt)	1997-09-30
CZ89397A3 (en)	1997-07-16
ATE168685T1 (de)	1998-08-15
WO1996010022A1 (en)	1996-04-04
AU696491B2 (en)	1998-09-10
US6730672B2 (en)	2004-05-04
DE69503647D1 (de)	1998-08-27
ES2119472T3 (es)	1998-10-01
PL319430A1 (en)	1997-08-04
DK0783500T3 (da)	1999-04-26
AU3530795A (en)	1996-04-19
HUT77769A (hu)	1998-08-28
IL115420A0 (en)	1995-12-31

Publication	Publication Date	Title
US6225309B1 (en)	2001-05-01	Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents
AU2006282456C1 (en)	2012-10-04	Novel pyridine derivative and pyrimidine derivative (3)
AU2005217325B2 (en)	2007-11-29	Novel pyridine derivative and pyrimidine derivative (1)
CN102227409B (zh)	2014-03-26	吡啶-3-甲酰胺衍生物
CA2806341C (en)	2020-03-24	Ampk-activating heterocyclic compounds and methods for using the same
DE69730490T2 (de)	2005-09-29	Aminoheterocyclische verbindungen als antithrombotisches oder antikoagulierendes mittel
US20070244088A1 (en)	2007-10-18	New Pyridine Analogues II
AU2007212429A1 (en)	2007-08-16	11-beta HSD1 inhibitors
CA2660699A1 (en)	2008-03-06	Pyridine compounds for treating gpr119 related disorders
WO1999016747A1 (en)	1999-04-08	Sulfonyl derivatives
US20080032992A1 (en)	2008-02-07	New Pyridine Analogues V
EP1192132A2 (de)	2002-04-03	Inhibitoren von serin proteasen
AU2007315955A1 (en)	2008-05-08	Pyridine carboxamides as 11-beta-HSD1 inhibitors
EA005943B1 (ru)	2005-08-25	Ингибиторы серинпротеазы
NZ522270A (en)	2004-03-26	Heterocyclic compounds as inhibitors of rotamase enzymes
KR20090031605A (ko)	2009-03-26	신규한 피리딘 유사체
MXPA97001841A (en)	1999-01-11	Amino heterocyclic derivatives as antitrombotic agents or anticoagulant
CN101243069A (zh)	2008-08-13	凝血酶抑制剂2-氧代-1,2,5,6-四氢吡啶衍生物
MX2008010099A (en)	2008-10-03	11-beta hsd1 inhibitors
MXPA99005822A (en)	2000-02-02	Piperazine compounds as inhibitors of mmp or tnf
MXPA01008067A (es)	2002-03-26	Derivados heterociclicos como inhibidores del factor xa