SI9620093A - Substituirane (sulfinska kislina, sulfonska kislina, sulfonilamino ali sulfinilamino) N-/(aminoiminometil)fenilalkil/-azaheterociklilamidne spojine - Google Patents
Substituirane (sulfinska kislina, sulfonska kislina, sulfonilamino ali sulfinilamino) N-/(aminoiminometil)fenilalkil/-azaheterociklilamidne spojine Download PDFInfo
- Publication number
- SI9620093A SI9620093A SI9620093A SI9620093A SI9620093A SI 9620093 A SI9620093 A SI 9620093A SI 9620093 A SI9620093 A SI 9620093A SI 9620093 A SI9620093 A SI 9620093A SI 9620093 A SI9620093 A SI 9620093A
- Authority
- SI
- Slovenia
- Prior art keywords
- trifluoroacetate
- oxopyrrolidin
- benzyl
- aminoiminomethyl
- amide
- Prior art date
Links
- -1 sulfinylamino Chemical group 0.000 title claims description 425
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 title description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 648
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 15
- 230000000694 effects Effects 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 242
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 189
- 229910052757 nitrogen Inorganic materials 0.000 claims description 173
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 129
- CKARHIGQRRNVFD-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OC)=CC=C21 CKARHIGQRRNVFD-UHFFFAOYSA-N 0.000 claims description 111
- 150000001408 amides Chemical class 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 40
- 150000002431 hydrogen Chemical group 0.000 claims description 37
- PFXMDSGRKNVHAA-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F PFXMDSGRKNVHAA-UHFFFAOYSA-N 0.000 claims description 35
- 230000015572 biosynthetic process Effects 0.000 claims description 33
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 19
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- SEDIJOBQZYCMRX-UHFFFAOYSA-N 4,5-dichlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC(Cl)=C(Cl)S1 SEDIJOBQZYCMRX-UHFFFAOYSA-N 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- FOIKGWJGRNNGQP-UHFFFAOYSA-N 6-methoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(OC)=CC=C21 FOIKGWJGRNNGQP-UHFFFAOYSA-N 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 9
- XCJLXFIGEMUOEE-UHFFFAOYSA-N acetamide;2,2,2-trifluoroacetic acid Chemical compound CC(N)=O.OC(=O)C(F)(F)F XCJLXFIGEMUOEE-UHFFFAOYSA-N 0.000 claims description 8
- XETFBTXVGCQYBD-UHFFFAOYSA-N methanamine;2,2,2-trifluoroacetic acid Chemical compound [NH3+]C.[O-]C(=O)C(F)(F)F XETFBTXVGCQYBD-UHFFFAOYSA-N 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- JANFYPHFIPGYTQ-UHFFFAOYSA-N dibenzofuran-2-sulfonic acid Chemical compound C1=CC=C2C3=CC(S(=O)(=O)O)=CC=C3OC2=C1 JANFYPHFIPGYTQ-UHFFFAOYSA-N 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- FPQOCCYRCZNLEJ-UHFFFAOYSA-N 3-fluoro-4-phenylbenzenesulfonic acid Chemical compound FC1=CC(S(=O)(=O)O)=CC=C1C1=CC=CC=C1 FPQOCCYRCZNLEJ-UHFFFAOYSA-N 0.000 claims description 4
- NAEFLOQMZCOADU-UQKRIMTDSA-N 4-[[(3s)-3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CSC(C(N)=N)=C1 NAEFLOQMZCOADU-UQKRIMTDSA-N 0.000 claims description 4
- RGKUDWDXKLGLJJ-FYZYNONXSA-N 4-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]pyridine-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=NC(C(N)=N)=C1 RGKUDWDXKLGLJJ-FYZYNONXSA-N 0.000 claims description 4
- VDHZTKHCEVXDOO-FERBBOLQSA-N 4-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CSC(C(N)=N)=C1 VDHZTKHCEVXDOO-FERBBOLQSA-N 0.000 claims description 4
- NUYLILFFMSAMHM-UHFFFAOYSA-N 4-pyridin-3-ylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=CN=C1 NUYLILFFMSAMHM-UHFFFAOYSA-N 0.000 claims description 4
- JLTUANWNGKWRQO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonyl chloride Chemical group C1=C(Cl)C=C2C(C)=C(S(Cl)(=O)=O)SC2=C1 JLTUANWNGKWRQO-UHFFFAOYSA-N 0.000 claims description 4
- HPUKOXOQHIMLHG-MERQFXBCSA-N N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O Chemical compound N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O HPUKOXOQHIMLHG-MERQFXBCSA-N 0.000 claims description 4
- PSMSAULBRKZYPJ-JIDHJSLPSA-N OC(=O)C(F)(F)F.COC1=CC=CC(C=2C=CC(=CC=2)S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.COC1=CC=CC(C=2C=CC(=CC=2)S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)=C1 PSMSAULBRKZYPJ-JIDHJSLPSA-N 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- OYQYQSQKSQRLFR-YCBFMBTMSA-N 2-[[(3s)-1-[(5-carbamimidoylthiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-(2-phenylethyl)acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC(=O)NCCC1=CC=CC=C1 OYQYQSQKSQRLFR-YCBFMBTMSA-N 0.000 claims description 3
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 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 claims description 3
- ADAKMYBJTQFVMB-UHFFFAOYSA-N 4-(3-methylphenyl)benzenesulfonic acid Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)S(O)(=O)=O)=C1 ADAKMYBJTQFVMB-UHFFFAOYSA-N 0.000 claims description 3
- UVMRQBRTXBKDCT-FGJQBABTSA-N 4-amino-3-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C(N)=N)=CC=C1N UVMRQBRTXBKDCT-FGJQBABTSA-N 0.000 claims description 3
- LFIBSJAAXWZLOV-FERBBOLQSA-N 5-chloro-N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-3-methyl-1-benzothiophene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CC=CC(C=NN)=C1 LFIBSJAAXWZLOV-FERBBOLQSA-N 0.000 claims description 3
- ODEQDYOTMMIYCC-UHFFFAOYSA-N COC(N)=O.OC(=O)C(F)(F)F Chemical compound COC(N)=O.OC(=O)C(F)(F)F ODEQDYOTMMIYCC-UHFFFAOYSA-N 0.000 claims description 3
- MFBILERJKRDWIH-FGJQBABTSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)N)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)N)=O)C=CC1 MFBILERJKRDWIH-FGJQBABTSA-N 0.000 claims description 3
- KOSRXDWVXPMSMD-FERBBOLQSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-2-ylthiophene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3SC(=CC=3)C=3N=CC=CC=3)CC2)=O)=C1 KOSRXDWVXPMSMD-FERBBOLQSA-N 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- NKBSYLJRVLPKJV-FTBISJDPSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C=NN)=C1 NKBSYLJRVLPKJV-FTBISJDPSA-N 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- RQUIWCGQCGPFBB-UHFFFAOYSA-N acetamide;2,2,2-trifluoroacetic acid Chemical compound CC(N)=O.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F RQUIWCGQCGPFBB-UHFFFAOYSA-N 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- XGVKSGFXYYTXDJ-YNMZEGNTSA-N 2-[[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-N-(2-phenylethyl)acetamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCCC2=CC=CC=C2)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 XGVKSGFXYYTXDJ-YNMZEGNTSA-N 0.000 claims description 2
- IXOFKWNMYWVYPS-JMAPEOGHSA-N 2-[[(3s)-1-[(2-carbamimidoylpyridin-4-yl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-(2-phenylethyl)acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(N=CC=2)C(N)=N)CC1)=O)CC(=O)NCCC1=CC=CC=C1 IXOFKWNMYWVYPS-JMAPEOGHSA-N 0.000 claims description 2
- KKPUHYNHYFSGJU-FERBBOLQSA-N 3-[[(3s)-2-oxo-3-(2-phenylethylsulfonylamino)pyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CC(CN2C([C@@H](NS(=O)(=O)CCC=3C=CC=CC=3)CC2)=O)=C1 KKPUHYNHYFSGJU-FERBBOLQSA-N 0.000 claims description 2
- SWYTZFVLVRAKNO-RMRYJAPISA-N 3-[[(3s)-2-oxo-3-[2-(pyridin-4-ylamino)ethylsulfonylamino]pyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC(=N)C1=CC=CC(CN2C([C@@H](NS(=O)(=O)CCNC=3C=CN=CC=3)CC2)=O)=C1 SWYTZFVLVRAKNO-RMRYJAPISA-N 0.000 claims description 2
- SRVMTFXBPLBKQW-FGJQBABTSA-N 3-amino-5-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(N)=CC(C(N)=N)=C1 SRVMTFXBPLBKQW-FGJQBABTSA-N 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- LPFNHKWZKHAOFK-RSAXXLAASA-N 4-[[(3S)-3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylmethylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NCS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CSC(C(N)=N)=C1 LPFNHKWZKHAOFK-RSAXXLAASA-N 0.000 claims description 2
- DKFBSNLAEFJLHM-BQAIUKQQSA-N 4-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonyl-(thiophen-3-ylmethyl)amino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC=1C=CSC=1 DKFBSNLAEFJLHM-BQAIUKQQSA-N 0.000 claims description 2
- SRRQGYUGZWLNCN-LMOVPXPDSA-N 4-[[(3s)-3-[[4-(2-chloro-6-nitrophenoxy)phenyl]sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](NS(=O)(=O)C=3C=CC(OC=4C(=CC=CC=4Cl)[N+]([O-])=O)=CC=3)CC2)=O)=C1 SRRQGYUGZWLNCN-LMOVPXPDSA-N 0.000 claims description 2
- OOJCAUVPXYMVBD-YCBFMBTMSA-N 4-[[(3s)-3-[benzyl-(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]pyridine-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(N=CC=2)C(N)=N)CC1)=O)CC1=CC=CC=C1 OOJCAUVPXYMVBD-YCBFMBTMSA-N 0.000 claims description 2
- XOXJLZQIZUJTHJ-UQIIZPHYSA-N 4-[[(3s)-3-[benzyl-(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC1=CC=CC=C1 XOXJLZQIZUJTHJ-UQIIZPHYSA-N 0.000 claims description 2
- LSDWQMOTHGPDIJ-FERBBOLQSA-N 4-[[(3s)-3-[methylsulfonyl(naphthalen-2-yl)amino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)N(S(=O)(=O)C)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CSC(C(N)=N)=C1 LSDWQMOTHGPDIJ-FERBBOLQSA-N 0.000 claims description 2
- KYEUOIMTDTWVJE-FTBISJDPSA-N 4-amino-3-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylmethylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NCS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C(N)=N)=CC=C1N KYEUOIMTDTWVJE-FTBISJDPSA-N 0.000 claims description 2
- HCISVIVZNALGKH-UQIIZPHYSA-N 5-[[(3s)-3-[benzyl-(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2SC(=CC=2)C(N)=N)CC1)=O)CC1=CC=CC=C1 HCISVIVZNALGKH-UQIIZPHYSA-N 0.000 claims description 2
- GXWGRQOMOLFZDN-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2C(C)=C(S(O)(=O)=O)SC2=C1 GXWGRQOMOLFZDN-UHFFFAOYSA-N 0.000 claims description 2
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- MXCVXJFNTSZXAD-LTCKWSDVSA-N CC(C(C=C(C=C1)Cl)=C1S1)=C1S(O)(=O)=O.CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O Chemical compound CC(C(C=C(C=C1)Cl)=C1S1)=C1S(O)(=O)=O.CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O MXCVXJFNTSZXAD-LTCKWSDVSA-N 0.000 claims description 2
- OGJQULGYYKDRHD-GXKRWWSZSA-N CN[C@@H](CCN1CC2=CC(C=NNOC)=CC=C2)C1=O.COC1=CC=C(C=C(C=C2)S(O)(=O)=O)C2=C1.OC(C(F)(F)F)=O Chemical compound CN[C@@H](CCN1CC2=CC(C=NNOC)=CC=C2)C1=O.COC1=CC=C(C=C(C=C2)S(O)(=O)=O)C2=C1.OC(C(F)(F)F)=O OGJQULGYYKDRHD-GXKRWWSZSA-N 0.000 claims description 2
- LATMXUHWNKOKDI-NTEVMMBTSA-N COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.NN=CC1=CC=CC(CN(CC[C@@H]2NCC3=CC([N+]([O-])=O)=CC=C3)C2=O)=C1.OC(C(F)(F)F)=O Chemical compound COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.NN=CC1=CC=CC(CN(CC[C@@H]2NCC3=CC([N+]([O-])=O)=CC=C3)C2=O)=C1.OC(C(F)(F)F)=O LATMXUHWNKOKDI-NTEVMMBTSA-N 0.000 claims description 2
- YMSOXJDTKYAEFV-RMRYJAPISA-N COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.NN=CC1=CC=CC(CN(C[C@@H]2NCC3=CC=CC=C3)C2=O)=C1.OC(C(F)(F)F)=O Chemical compound COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.NN=CC1=CC=CC(CN(C[C@@H]2NCC3=CC=CC=C3)C2=O)=C1.OC(C(F)(F)F)=O YMSOXJDTKYAEFV-RMRYJAPISA-N 0.000 claims description 2
- 208000005189 Embolism Diseases 0.000 claims description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 2
- XBLZIVRCHOKATF-FYZYNONXSA-N FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC=1C=C(SC1)C(=N)N)=O Chemical compound FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC=1C=C(SC1)C(=N)N)=O XBLZIVRCHOKATF-FYZYNONXSA-N 0.000 claims description 2
- KURIZQKRORFWPW-NTEVMMBTSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC=1C=C(SC1)C(=N)N)=O Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC=1C=C(SC1)C(=N)N)=O KURIZQKRORFWPW-NTEVMMBTSA-N 0.000 claims description 2
- XGVCHQQUMUUYKM-UJXPALLWSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC(=CC=C2)N)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC(=CC=C2)N)=O)C=CC1 XGVCHQQUMUUYKM-UJXPALLWSA-N 0.000 claims description 2
- LNJOSHSHPKOMSB-FGJQBABTSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C[C@H](CC2)NS(=O)(=O)C2=CC3=CC=CC=C3C=C2)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C[C@H](CC2)NS(=O)(=O)C2=CC3=CC=CC=C3C=C2)C=CC1 LNJOSHSHPKOMSB-FGJQBABTSA-N 0.000 claims description 2
- KREXWMQEFYDYQH-CZCBIWLKSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCCC2=CC=CC=C2)S(=O)(=O)C2=CC3=CC=CC=C3C=C2)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCCC2=CC=CC=C2)S(=O)(=O)C2=CC3=CC=CC=C3C=C2)=O)C=CC1 KREXWMQEFYDYQH-CZCBIWLKSA-N 0.000 claims description 2
- DGTUVYAXDYEJJL-JMAPEOGHSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=C(C=CC=C2)[N+](=O)[O-])=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=C(C=CC=C2)[N+](=O)[O-])=O)C=CC1 DGTUVYAXDYEJJL-JMAPEOGHSA-N 0.000 claims description 2
- MTSLBGOYZKKCAD-BOXHHOBZSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)O)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)O)=O)C=CC1 MTSLBGOYZKKCAD-BOXHHOBZSA-N 0.000 claims description 2
- XSTFUJGDAHCYAR-VOEROWCCSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2C(C=CC=C2)(OC2=CC=CC=C2[N+](=O)[O-])Cl)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2C(C=CC=C2)(OC2=CC=CC=C2[N+](=O)[O-])Cl)=O)C=CC1 XSTFUJGDAHCYAR-VOEROWCCSA-N 0.000 claims description 2
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- UYILOPMDMLMLGB-BOXHHOBZSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4CCCCC4=CC=3)CC2)=O)=C1 UYILOPMDMLMLGB-BOXHHOBZSA-N 0.000 claims description 2
- UMQQZKPPZYVKBT-BDQAORGHSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]quinoline-6-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC=NC4=CC=3)CC2)=O)=C1 UMQQZKPPZYVKBT-BDQAORGHSA-N 0.000 claims description 2
- VGJJPBRMUANHMV-BOXHHOBZSA-N N-[(3S)-1-[(4-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C=NN)=CC=C1CN1C(=O)[C@@H](NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC1 VGJJPBRMUANHMV-BOXHHOBZSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- MRTTYKVNJDOIEZ-FTBISJDPSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)C)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)C)CN1CC1=CC=CC(C=NN)=C1 MRTTYKVNJDOIEZ-FTBISJDPSA-N 0.000 claims description 2
- NGVRHRWKHXHNLZ-BOXHHOBZSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)C(=O)N1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)C(=O)N1CC1=CC=CC(C=NN)=C1 NGVRHRWKHXHNLZ-BOXHHOBZSA-N 0.000 claims description 2
- PPWIGVRIZVXAMY-AXESWQTNSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)OC=3C=CC=CC=3)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)OC=3C=CC=CC=3)CC2)=O)=C1 PPWIGVRIZVXAMY-AXESWQTNSA-N 0.000 claims description 2
- PNFKRMLGYMIFMQ-BDQAORGHSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)N3CC4=CC=CC=C4CC3)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)N3CC4=CC=CC=C4CC3)CC2)=O)=C1 PNFKRMLGYMIFMQ-BDQAORGHSA-N 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 208000001435 Thromboembolism Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 206010053648 Vascular occlusion Diseases 0.000 claims description 2
- 206010047139 Vasoconstriction Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 210000005249 arterial vasculature Anatomy 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 238000007887 coronary angioplasty Methods 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 210000003127 knee Anatomy 0.000 claims description 2
- 230000007774 longterm Effects 0.000 claims description 2
- 210000003141 lower extremity Anatomy 0.000 claims description 2
- UEYDDASXCIIWPL-KRWDZBQOSA-N methyl 2-[[(3s)-1-[(4-carbamimidoylthiophen-2-yl)methyl]-2-oxopyrrolidin-3-yl]-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]amino]acetate Chemical compound C([C@@H](C1=O)N(CC(=O)OC)S(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CC(C(N)=N)=CS1 UEYDDASXCIIWPL-KRWDZBQOSA-N 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- XBOASQFJGNMWLQ-FTBISJDPSA-N n-[(3s)-1-[[3-(aminomethyl)phenyl]methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(CN)=C1 XBOASQFJGNMWLQ-FTBISJDPSA-N 0.000 claims description 2
- YABSZVYEGXLSNB-SNYZSRNZSA-N n-benzyl-2-[[(3s)-1-[(5-carbamimidoylthiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC(=O)NCC1=CC=CC=C1 YABSZVYEGXLSNB-SNYZSRNZSA-N 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- ZSZBVCQVYPCNIF-UHFFFAOYSA-N propanamide;2,2,2-trifluoroacetic acid Chemical compound CCC(N)=O.OC(=O)C(F)(F)F ZSZBVCQVYPCNIF-UHFFFAOYSA-N 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- IVIIAEVMQHEPAY-UHFFFAOYSA-N tridodecyl phosphite Chemical compound CCCCCCCCCCCCOP(OCCCCCCCCCCCC)OCCCCCCCCCCCC IVIIAEVMQHEPAY-UHFFFAOYSA-N 0.000 claims description 2
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 2
- 210000005166 vasculature Anatomy 0.000 claims description 2
- 230000025033 vasoconstriction Effects 0.000 claims description 2
- 210000003462 vein Anatomy 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 3
- LDJAAPXNPMYLFA-UHFFFAOYSA-N thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CS1 LDJAAPXNPMYLFA-UHFFFAOYSA-N 0.000 claims 3
- PSMPKMMRMHZGBQ-NSHDSACASA-N C1CN(C(=O)[C@H]1N)CC2=CC(=CC=C2)C=NN Chemical compound C1CN(C(=O)[C@H]1N)CC2=CC(=CC=C2)C=NN PSMPKMMRMHZGBQ-NSHDSACASA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- SJSRROADNKKXJN-FERBBOLQSA-N 2-[[(3s)-1-[(5-carbamimidoylthiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-(4,5-dichlorothiophen-2-yl)sulfonylamino]-n-(2-phenylethyl)acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC(=O)NCCC=3C=CC=CC=3)S(=O)(=O)C=3SC(Cl)=C(Cl)C=3)CC2)=O)=C1 SJSRROADNKKXJN-FERBBOLQSA-N 0.000 claims 1
- YYBTWQPBNZCADF-KRWDZBQOSA-N 3-[[(3s)-2-oxo-3-[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]pyrrolidin-1-yl]methyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3SC(=CC=3)C=3N=CC=CC=3)CC2)=O)=C1 YYBTWQPBNZCADF-KRWDZBQOSA-N 0.000 claims 1
- OOQILWQLMQMCTL-BDQAORGHSA-N 4-[[(3S)-3-[(7-methoxynaphthalen-2-yl)sulfonylmethylamino]-2-oxopyrrolidin-1-yl]methyl]pyridine-2-carboximidamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NCS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=NC(C(N)=N)=C1 OOQILWQLMQMCTL-BDQAORGHSA-N 0.000 claims 1
- KTHHXNVRFKTMND-RSAXXLAASA-N 4-[[(3s)-3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]pyridine-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CC=NC(C(N)=N)=C1 KTHHXNVRFKTMND-RSAXXLAASA-N 0.000 claims 1
- YRDOJWMRCBPRCU-RMRYJAPISA-N 4-[[(3s)-3-[(6-aminonaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;dihydrochloride Chemical compound Cl.Cl.S1C(C(=N)N)=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(N)=CC4=CC=3)CC2)=O)=C1 YRDOJWMRCBPRCU-RMRYJAPISA-N 0.000 claims 1
- NVHBZASBXMXHOU-ASMAMLKCSA-N 4-[[(3s)-3-[(7-aminonaphthalen-2-yl)sulfonyl-benzylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC=3C=CC=CC=3)S(=O)(=O)C=3C=C4C=C(N)C=CC4=CC=3)CC2)=O)=C1 NVHBZASBXMXHOU-ASMAMLKCSA-N 0.000 claims 1
- XPYLLZDJKWAGNP-NTISSMGPSA-N 4-[[(3s)-3-[benzyl-(4,5-dichlorothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC=3C=CC=CC=3)S(=O)(=O)C=3SC(Cl)=C(Cl)C=3)CC2)=O)=C1 XPYLLZDJKWAGNP-NTISSMGPSA-N 0.000 claims 1
- ASVYULXOOYAQPJ-FYZYNONXSA-N 4-amino-3-[[(3s)-3-[(4-tert-butylphenyl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)N[C@@H]1C(=O)N(CC=2C(=CC=C(C=2)C(N)=N)N)CC1 ASVYULXOOYAQPJ-FYZYNONXSA-N 0.000 claims 1
- GOSCQCGNFATPPM-FERBBOLQSA-N 5-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=C(C(N)=N)S1 GOSCQCGNFATPPM-FERBBOLQSA-N 0.000 claims 1
- ZELYYTVHQRSLGT-BQAIUKQQSA-N 7-ethyl-N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)CC)CN1CC1=CC=CC(C=NN)=C1 ZELYYTVHQRSLGT-BQAIUKQQSA-N 0.000 claims 1
- FLFRAFPLANTDFS-BDQAORGHSA-N 8-chloro-N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C(=C3C=2)Cl)OC)CN1CC1=CC=CC(C=NN)=C1 FLFRAFPLANTDFS-BDQAORGHSA-N 0.000 claims 1
- BYXPQFNGADEFPM-UHFFFAOYSA-N C1=CC(=CC2=C3CCCCC3=CC=C12)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound C1=CC(=CC2=C3CCCCC3=CC=C12)S(=O)(=O)O.FC(C(=O)O)(F)F BYXPQFNGADEFPM-UHFFFAOYSA-N 0.000 claims 1
- ZSPHVDVDUMSBGJ-LTCKWSDVSA-N CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.Cl.Cl Chemical compound CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.Cl.Cl ZSPHVDVDUMSBGJ-LTCKWSDVSA-N 0.000 claims 1
- RYKYHTGXZFMEPO-UHFFFAOYSA-N COC(C(F)(F)F)=O.C(N)(O)=O Chemical compound COC(C(F)(F)F)=O.C(N)(O)=O RYKYHTGXZFMEPO-UHFFFAOYSA-N 0.000 claims 1
- WGFAPPBNUYJQLQ-QHELBMECSA-N COC1=CC=CC(C2(C=CC=CC2)S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)=N1 Chemical compound COC1=CC=CC(C2(C=CC=CC2)S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)=N1 WGFAPPBNUYJQLQ-QHELBMECSA-N 0.000 claims 1
- QTEOSMVUYBCUCR-UHFFFAOYSA-N ClC1=CC=C(S1)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound ClC1=CC=C(S1)S(=O)(=O)O.FC(C(=O)O)(F)F QTEOSMVUYBCUCR-UHFFFAOYSA-N 0.000 claims 1
- QRTPFBFUZAIJBE-GXKRWWSZSA-N FC(C(=O)O)(F)F.C(#N)NN=CC=1C=C(CN2C([C@H](CC2)NC)=O)C=CC1.COC=1C=C2C=CC(=CC2=CC1)S(=O)(=O)O Chemical compound FC(C(=O)O)(F)F.C(#N)NN=CC=1C=C(CN2C([C@H](CC2)NC)=O)C=CC1.COC=1C=C2C=CC(=CC2=CC1)S(=O)(=O)O QRTPFBFUZAIJBE-GXKRWWSZSA-N 0.000 claims 1
- SQDLKJDHOBOTPS-BDQAORGHSA-N FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC(=CS1)C(=N)N)=O Chemical compound FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC(=CS1)C(=N)N)=O SQDLKJDHOBOTPS-BDQAORGHSA-N 0.000 claims 1
- QLROFPQYNZPJHK-FYZYNONXSA-N FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC=C(S1)C(=N)N)=O Chemical compound FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC=C(S1)C(=N)N)=O QLROFPQYNZPJHK-FYZYNONXSA-N 0.000 claims 1
- RMDOMQOXOHVXCB-UJXPALLWSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)N)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)N)=O)C=CC1 RMDOMQOXOHVXCB-UJXPALLWSA-N 0.000 claims 1
- ZQHNLKVUTFQYTI-UQIIZPHYSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)N(C)C)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)N(C)C)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 ZQHNLKVUTFQYTI-UQIIZPHYSA-N 0.000 claims 1
- IRQRAZFDOCXQKE-UCRKPPETSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NC2CC3=CC=CC=C3C2)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NC2CC3=CC=CC=C3C2)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 IRQRAZFDOCXQKE-UCRKPPETSA-N 0.000 claims 1
- MPTFFWXYVITTCJ-UQIIZPHYSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCC)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCC)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 MPTFFWXYVITTCJ-UQIIZPHYSA-N 0.000 claims 1
- MRQFYDABMZCZLM-CZCBIWLKSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCC2=CC=CC=C2)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCC2=CC=CC=C2)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1 MRQFYDABMZCZLM-CZCBIWLKSA-N 0.000 claims 1
- MUPXGPKWBWACFA-UCRKPPETSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCCC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C2=CC=CC=C2)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(CC(=O)NCCC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C2=CC=CC=C2)=O)C=CC1 MUPXGPKWBWACFA-UCRKPPETSA-N 0.000 claims 1
- NDKCBVHFROZHSR-JMAPEOGHSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)[N+](=O)[O-])=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)[N+](=O)[O-])=O)C=CC1 NDKCBVHFROZHSR-JMAPEOGHSA-N 0.000 claims 1
- SBXOZKPZNSZOMT-BOXHHOBZSA-N FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)O)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)O)=O)C=CC1 SBXOZKPZNSZOMT-BOXHHOBZSA-N 0.000 claims 1
- CBTIAQXKRXXQOQ-JIDHJSLPSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxoazepan-3-yl]-7-methoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CCCN1CC1=CC=CC(C=NN)=C1 CBTIAQXKRXXQOQ-JIDHJSLPSA-N 0.000 claims 1
- LKLRSOMXHGHIES-BOXHHOBZSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxoazetidin-3-yl]-7-methoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)N1CC1=CC=CC(C=NN)=C1 LKLRSOMXHGHIES-BOXHHOBZSA-N 0.000 claims 1
- ANPMQVDEBFEXIU-FYZYNONXSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-2-methoxyquinoline-7-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(N=C3C=2)OC)CN1CC1=CC=CC(C=NN)=C1 ANPMQVDEBFEXIU-FYZYNONXSA-N 0.000 claims 1
- KPSBUCMUVWEHQO-JIDHJSLPSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-4-(3-methylphenyl)benzenesulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC=CC(C=2C=CC(=CC=2)S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)=C1 KPSBUCMUVWEHQO-JIDHJSLPSA-N 0.000 claims 1
- JZXDBQBFGODLDQ-BOXHHOBZSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-6,7-dimethoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC=C3C=C(C(=CC3=C2)OC)OC)CN1CC1=CC=CC(C=NN)=C1 JZXDBQBFGODLDQ-BOXHHOBZSA-N 0.000 claims 1
- MIONUFUSONUDPQ-JCOPYZAKSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-7-phenylmethoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=C(OCC=5C=CC=CC=5)C=CC4=CC=3)CC2)=O)=C1 MIONUFUSONUDPQ-JCOPYZAKSA-N 0.000 claims 1
- PEEMLQRBMFADOG-BDQAORGHSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]benzo[f][1,3]benzodioxole-6-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=C5OCOC5=CC4=CC=3)CC2)=O)=C1 PEEMLQRBMFADOG-BDQAORGHSA-N 0.000 claims 1
- FFDFENVUPNNLGC-FTBISJDPSA-N N-[(3S)-1-[(4-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=C(C=NN)C=C1 FFDFENVUPNNLGC-FTBISJDPSA-N 0.000 claims 1
- YWXTWLRVWBNWIV-QFIPXVFZSA-N NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=CC(=CC=3)C=3C=CN=CC=3)CC2)=O)=C1 Chemical compound NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=CC(=CC=3)C=3C=CN=CC=3)CC2)=O)=C1 YWXTWLRVWBNWIV-QFIPXVFZSA-N 0.000 claims 1
- UCHNCUYDKVEMFV-FQEVSTJZSA-N NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)N)=O)C=CC1 Chemical compound NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)N)=O)C=CC1 UCHNCUYDKVEMFV-FQEVSTJZSA-N 0.000 claims 1
- LQWWBOJWQIQDBA-FQEVSTJZSA-N NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C=2C=C3C=CC=NC3=CC2)=O)C=CC1 Chemical compound NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C=2C=C3C=CC=NC3=CC2)=O)C=CC1 LQWWBOJWQIQDBA-FQEVSTJZSA-N 0.000 claims 1
- SAJUTOPUSPLKCC-BDQAORGHSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)OC)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)OC)CN1CC1=CC=CC(C=NN)=C1 SAJUTOPUSPLKCC-BDQAORGHSA-N 0.000 claims 1
- QLSKPEFSUBNIHI-BQAIUKQQSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OCC)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OCC)CN1CC1=CC=CC(C=NN)=C1 QLSKPEFSUBNIHI-BQAIUKQQSA-N 0.000 claims 1
- XEMMMLHWHRMDNI-BDQAORGHSA-N OC(=O)C(F)(F)F.CN1C=CN=C1C1=CC=C(S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)C=C1 Chemical compound OC(=O)C(F)(F)F.CN1C=CN=C1C1=CC=C(S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)C=C1 XEMMMLHWHRMDNI-BDQAORGHSA-N 0.000 claims 1
- XOARGDFSSGZUHP-BQAIUKQQSA-N OC(=O)C(F)(F)F.COC1=CC=CC=C1C1=CC=C(S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)C=C1 Chemical compound OC(=O)C(F)(F)F.COC1=CC=CC=C1C1=CC=C(S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=NN)C=CC=3)CC2)=O)C=C1 XOARGDFSSGZUHP-BQAIUKQQSA-N 0.000 claims 1
- YBVDZPABCBSXEY-UHFFFAOYSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C(C(NS(=O)(=O)C=3C=C4C=CC=CC4=CC=3)CCC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C(C(NS(=O)(=O)C=3C=C4C=CC=CC4=CC=3)CCC2)=O)=C1 YBVDZPABCBSXEY-UHFFFAOYSA-N 0.000 claims 1
- GOWSSNKUORTWFJ-GTVPGWBMSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)C=3C=[N+]([O-])C=CC=3)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)C=3C=[N+]([O-])C=CC=3)CC2)=O)=C1 GOWSSNKUORTWFJ-GTVPGWBMSA-N 0.000 claims 1
- BKSPDZSTIVXCHF-HAABMKSFSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)OC=3C(=CC=CN=3)Cl)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C3(C=CC=CC3)OC=3C(=CC=CN=3)Cl)CC2)=O)=C1 BKSPDZSTIVXCHF-HAABMKSFSA-N 0.000 claims 1
- BIMQSYXGQFKQPR-BOXHHOBZSA-N OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC=CC4=CC=3)CC2)=O)=C1 Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC=CC4=CC=3)CC2)=O)=C1 BIMQSYXGQFKQPR-BOXHHOBZSA-N 0.000 claims 1
- 201000005702 Pertussis Diseases 0.000 claims 1
- 230000003187 abdominal effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- AKMQTOYEZRXRQZ-UHFFFAOYSA-N furan-2-carboximidamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.O1C(=CC=C1)C(=N)N AKMQTOYEZRXRQZ-UHFFFAOYSA-N 0.000 claims 1
- 238000001631 haemodialysis Methods 0.000 claims 1
- 230000000322 hemodialysis Effects 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 238000012423 maintenance Methods 0.000 claims 1
- FNKLGGIAXFTGTF-UHFFFAOYSA-N methyl acetate;2,2,2-trifluoroacetic acid Chemical compound COC(C)=O.OC(=O)C(F)(F)F FNKLGGIAXFTGTF-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 97
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 230000001668 ameliorated effect Effects 0.000 abstract 1
- 230000004962 physiological condition Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 430
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 282
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 267
- 229910001868 water Inorganic materials 0.000 description 257
- 239000000243 solution Substances 0.000 description 250
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 247
- 235000019439 ethyl acetate Nutrition 0.000 description 213
- 239000007787 solid Substances 0.000 description 212
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 197
- 239000012043 crude product Substances 0.000 description 188
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 184
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 176
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 description 132
- 239000000047 product Substances 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- 238000004440 column chromatography Methods 0.000 description 92
- 238000000921 elemental analysis Methods 0.000 description 92
- 238000004007 reversed phase HPLC Methods 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- 239000012044 organic layer Substances 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 52
- 239000006260 foam Substances 0.000 description 51
- 239000007858 starting material Substances 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 239000002253 acid Substances 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 159000000000 sodium salts Chemical class 0.000 description 38
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 36
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000543 intermediate Substances 0.000 description 33
- ZHASTWZTZMFNOJ-MERQFXBCSA-N 3-[[(3s)-3-amino-2-oxopyrrolidin-1-yl]methyl]benzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1CC1=CC=CC(C#N)=C1 ZHASTWZTZMFNOJ-MERQFXBCSA-N 0.000 description 30
- 150000001409 amidines Chemical class 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 28
- 229920006395 saturated elastomer Polymers 0.000 description 28
- WUEQPLNKVFNLRV-QFIPXVFZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C#N)=C1 WUEQPLNKVFNLRV-QFIPXVFZSA-N 0.000 description 21
- 229940086542 triethylamine Drugs 0.000 description 21
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- 238000000034 method Methods 0.000 description 19
- 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 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- URGYOOCIIWNIEX-NSHDSACASA-N 3-[[(3s)-3-amino-2-oxopyrrolidin-1-yl]methyl]benzonitrile Chemical compound O=C1[C@@H](N)CCN1CC1=CC=CC(C#N)=C1 URGYOOCIIWNIEX-NSHDSACASA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 229910052708 sodium Inorganic materials 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 229920006063 Lamide® Polymers 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
- 229940117803 phenethylamine Drugs 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 230000001476 alcoholic effect Effects 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 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 9
- 239000012312 sodium hydride Substances 0.000 description 9
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 9
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 8
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- MVEOHWRUBFWKJY-UHFFFAOYSA-N 7-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(O)=CC=C21 MVEOHWRUBFWKJY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002946 cyanobenzyl group Chemical group 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 5
- BLKOSTJSUMJMSR-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)S1 BLKOSTJSUMJMSR-UHFFFAOYSA-N 0.000 description 5
- VVPHSMHEYVOVLH-UHFFFAOYSA-N 6-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(O)=CC=C21 VVPHSMHEYVOVLH-UHFFFAOYSA-N 0.000 description 5
- 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 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000003146 anticoagulant agent Substances 0.000 description 5
- 125000004104 aryloxy group Chemical group 0.000 description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 5
- XDFORSMZCYHNBG-UHFFFAOYSA-N benzonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=CC=C1 XDFORSMZCYHNBG-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 5
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- 239000011592 zinc chloride Substances 0.000 description 5
- 235000005074 zinc chloride Nutrition 0.000 description 5
- LDRWTKQWSXGSTM-LBPRGKRZSA-N (3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(O)=O)C(=O)OCC1=CC=CC=C1 LDRWTKQWSXGSTM-LBPRGKRZSA-N 0.000 description 4
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- IIQVZSJNEOWJIY-UHFFFAOYSA-N 3,4-dihydro-1h-isoquinoline-2-sulfonic acid Chemical compound C1=CC=C2CN(S(=O)(=O)O)CCC2=C1 IIQVZSJNEOWJIY-UHFFFAOYSA-N 0.000 description 4
- XDTYUYVIGLIFCW-UHFFFAOYSA-N 4-phenylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=CC=C1 XDTYUYVIGLIFCW-UHFFFAOYSA-N 0.000 description 4
- LRKJKHNZRCAUSV-UHFFFAOYSA-N 4-pyridin-4-ylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=NC=C1 LRKJKHNZRCAUSV-UHFFFAOYSA-N 0.000 description 4
- RRELHGZMPGGKMS-UHFFFAOYSA-N 5-chloro-6-methoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=C(Cl)C(OC)=CC=C21 RRELHGZMPGGKMS-UHFFFAOYSA-N 0.000 description 4
- XFKLOCCEYJPASF-UHFFFAOYSA-N 7-(phenylmethoxycarbonylamino)naphthalene-2-sulfonic acid Chemical compound C=1C2=CC(S(=O)(=O)O)=CC=C2C=CC=1NC(=O)OCC1=CC=CC=C1 XFKLOCCEYJPASF-UHFFFAOYSA-N 0.000 description 4
- OKAUOXITMZTUOJ-UHFFFAOYSA-N 7-aminonaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 OKAUOXITMZTUOJ-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000004442 acylamino group Chemical group 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 4
- 239000012456 homogeneous solution Substances 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- YFMJTLUPSMCTOQ-UHFFFAOYSA-N isoquinoline-5-sulfonic acid Chemical compound N1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 YFMJTLUPSMCTOQ-UHFFFAOYSA-N 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- DBCQJALPCJPHFS-QFIPXVFZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-6-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)OC)CN1CC1=CC=CC(C#N)=C1 DBCQJALPCJPHFS-QFIPXVFZSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 4
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000005270 trialkylamine group Chemical group 0.000 description 4
- BIKLVMHYAOBYOU-UHFFFAOYSA-N (7-ethylnaphthalen-2-yl)-trimethylstannane Chemical compound C1=CC([Sn](C)(C)C)=CC2=CC(CC)=CC=C21 BIKLVMHYAOBYOU-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 3
- SVDZWRPQYYCMGG-UHFFFAOYSA-N 2,4-diaminoquinazoline-6-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=NC(N)=NC(N)=C21 SVDZWRPQYYCMGG-UHFFFAOYSA-N 0.000 description 3
- RKIVBXUNCCKPJO-UHFFFAOYSA-N 2-methoxyquinoline-7-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=NC(OC)=CC=C21 RKIVBXUNCCKPJO-UHFFFAOYSA-N 0.000 description 3
- ITSMLVBLBSCNPN-UHFFFAOYSA-N 4-(2-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=CC=C1C1=CC=C(S(O)(=O)=O)C=C1 ITSMLVBLBSCNPN-UHFFFAOYSA-N 0.000 description 3
- QWZZUZAIHNZLEN-UHFFFAOYSA-N 5-pyridin-2-ylthiophene-2-sulfonic acid Chemical compound S1C(S(=O)(=O)O)=CC=C1C1=CC=CC=N1 QWZZUZAIHNZLEN-UHFFFAOYSA-N 0.000 description 3
- FTPWWZQLXRBLHQ-UHFFFAOYSA-N 6-amino-5-chloronaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=C(Cl)C(N)=CC=C21 FTPWWZQLXRBLHQ-UHFFFAOYSA-N 0.000 description 3
- HNCOXIKXVHLGMB-UHFFFAOYSA-N 7-[methyl(phenylmethoxycarbonyl)amino]naphthalene-2-sulfonic acid Chemical compound C=1C=C2C=CC(S(O)(=O)=O)=CC2=CC=1N(C)C(=O)OCC1=CC=CC=C1 HNCOXIKXVHLGMB-UHFFFAOYSA-N 0.000 description 3
- DLEXGQNBBCPGTH-UHFFFAOYSA-N 7-ethoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OCC)=CC=C21 DLEXGQNBBCPGTH-UHFFFAOYSA-N 0.000 description 3
- AMTXWXZUNMMYFQ-UHFFFAOYSA-N 7-ethylnaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(CC)=CC=C21 AMTXWXZUNMMYFQ-UHFFFAOYSA-N 0.000 description 3
- LUGQQBPUAULKPK-UHFFFAOYSA-N 7-methylnaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(C)=CC=C21 LUGQQBPUAULKPK-UHFFFAOYSA-N 0.000 description 3
- FOHILZARZALLTM-UHFFFAOYSA-N 8-chloro-7-methoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=C(Cl)C(OC)=CC=C21 FOHILZARZALLTM-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 125000003435 aroyl group Chemical group 0.000 description 3
- 125000005239 aroylamino group Chemical group 0.000 description 3
- HLMGQSNPAYICCF-UHFFFAOYSA-N benzo[f][1,3]benzodioxole-6-sulfonic acid Chemical compound C1=C2OCOC2=CC2=CC(S(=O)(=O)O)=CC=C21 HLMGQSNPAYICCF-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000008241 heterogeneous mixture Substances 0.000 description 3
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- GXPHBSPDHDMGSY-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 GXPHBSPDHDMGSY-NRFANRHFSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- BQWSRNKFRAPUAH-UHFFFAOYSA-N (3-cyanophenyl)methylazanium;chloride Chemical compound Cl.NCC1=CC=CC(C#N)=C1 BQWSRNKFRAPUAH-UHFFFAOYSA-N 0.000 description 2
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- HAENQBPGVQJEAP-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-7-sulfonic acid;3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F.C1CNCC2=CC(S(=O)(=O)O)=CC=C21 HAENQBPGVQJEAP-UHFFFAOYSA-N 0.000 description 2
- PEZWXANTSFRABD-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride;3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F.C1CNCC2=CC(S(=O)(=O)Cl)=CC=C21 PEZWXANTSFRABD-UHFFFAOYSA-N 0.000 description 2
- SNEXWZZSJSYNHR-UHFFFAOYSA-N 1-(2-bromoethyl)-2-cyclopropylbenzene Chemical compound BrCCC1=CC=CC=C1C1CC1 SNEXWZZSJSYNHR-UHFFFAOYSA-N 0.000 description 2
- PNQPQIIGGUWDPR-UHFFFAOYSA-N 1-(3-chloropyridin-2-yl)oxycyclohexa-2,4-diene-1-sulfonic acid Chemical compound N=1C=CC=C(Cl)C=1OC1(S(=O)(=O)O)CC=CC=C1 PNQPQIIGGUWDPR-UHFFFAOYSA-N 0.000 description 2
- DVFZTLPDJYSVOQ-UHFFFAOYSA-N 1-bromo-4-(2-methoxyphenyl)benzene Chemical compound COC1=CC=CC=C1C1=CC=C(Br)C=C1 DVFZTLPDJYSVOQ-UHFFFAOYSA-N 0.000 description 2
- CRRUGYDDEMGVDY-UHFFFAOYSA-N 1-bromoethylbenzene Chemical compound CC(Br)C1=CC=CC=C1 CRRUGYDDEMGVDY-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- YEIZCIHTAAWELE-UHFFFAOYSA-N 2,4-diaminoquinazoline-6-sulfonyl chloride;sulfuric acid Chemical compound OS(O)(=O)=O.C1=C(S(Cl)(=O)=O)C=CC2=NC(N)=NC(N)=C21 YEIZCIHTAAWELE-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- RUHJZSZTSCSTCC-UHFFFAOYSA-N 2-(bromomethyl)naphthalene Chemical compound C1=CC=CC2=CC(CBr)=CC=C21 RUHJZSZTSCSTCC-UHFFFAOYSA-N 0.000 description 2
- GJUCEJSGLTUDBP-UHFFFAOYSA-N 2-ethyl-7-(trifluoromethylsulfonyl)naphthalene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC2=CC(CC)=CC=C21 GJUCEJSGLTUDBP-UHFFFAOYSA-N 0.000 description 2
- IZQPFGFFOUIMRX-UHFFFAOYSA-N 2-ethyl-7-methoxynaphthalene Chemical compound C1=CC(OC)=CC2=CC(CC)=CC=C21 IZQPFGFFOUIMRX-UHFFFAOYSA-N 0.000 description 2
- UCPTZHVHPVIYTF-UHFFFAOYSA-N 2-methoxy-7-(trifluoromethylsulfonyl)naphthalene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC2=CC(OC)=CC=C21 UCPTZHVHPVIYTF-UHFFFAOYSA-N 0.000 description 2
- ACXAMVZBGIWPPD-UHFFFAOYSA-N 2-methoxy-7-methylnaphthalene Chemical compound C1=CC(C)=CC2=CC(OC)=CC=C21 ACXAMVZBGIWPPD-UHFFFAOYSA-N 0.000 description 2
- STVJRVNXSOTHGH-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinoline-7-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2CN(C)CCC2=C1 STVJRVNXSOTHGH-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
- XFKPORAVEUOIRF-UHFFFAOYSA-N 3-(aminomethyl)benzonitrile Chemical compound NCC1=CC=CC(C#N)=C1 XFKPORAVEUOIRF-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- UFPIRWXIODIJGC-UHFFFAOYSA-N 3-[(4-amino-2-oxopyrrolidin-1-yl)methyl]benzonitrile;hydrochloride Chemical compound Cl.O=C1CC(N)CN1CC1=CC=CC(C#N)=C1 UFPIRWXIODIJGC-UHFFFAOYSA-N 0.000 description 2
- BDAQHLRPAUPBNA-UHFFFAOYSA-N 3-fluoro-4-phenylbenzenesulfonyl chloride Chemical compound FC1=CC(S(Cl)(=O)=O)=CC=C1C1=CC=CC=C1 BDAQHLRPAUPBNA-UHFFFAOYSA-N 0.000 description 2
- YACPNVHTJGEYHQ-ZDUSSCGKSA-N 4,5-dichloro-n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]thiophene-2-sulfonamide Chemical compound S1C(Cl)=C(Cl)C=C1S(=O)(=O)N[C@@H]1C(=O)N(CC=2C=C(C=CC=2)C#N)CC1 YACPNVHTJGEYHQ-ZDUSSCGKSA-N 0.000 description 2
- UESYVKKKRJARGN-UHFFFAOYSA-N 4-(1-oxidopyridin-1-ium-3-yl)benzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=C[N+]([O-])=C1 UESYVKKKRJARGN-UHFFFAOYSA-N 0.000 description 2
- IIGVTBXGSGACRA-UHFFFAOYSA-N 4-(3-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)S(O)(=O)=O)=C1 IIGVTBXGSGACRA-UHFFFAOYSA-N 0.000 description 2
- DVQBUJTYQXKLKZ-UHFFFAOYSA-N 4-(3-methoxyphenyl)benzenesulfonyl chloride Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)S(Cl)(=O)=O)=C1 DVQBUJTYQXKLKZ-UHFFFAOYSA-N 0.000 description 2
- QREZLLYPLRPULF-UHFFFAOYSA-N 4-(aminomethyl)benzonitrile;hydron;chloride Chemical compound Cl.NCC1=CC=C(C#N)C=C1 QREZLLYPLRPULF-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
- QYAANYADJMPKHC-MERQFXBCSA-N 4-[[(3s)-3-amino-2-oxopyrrolidin-1-yl]methyl]benzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1CC1=CC=C(C#N)C=C1 QYAANYADJMPKHC-MERQFXBCSA-N 0.000 description 2
- MBZDCUMFFPWLTJ-UHFFFAOYSA-N 4-amino-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1N MBZDCUMFFPWLTJ-UHFFFAOYSA-N 0.000 description 2
- MYPXYQMABPTFFN-UHFFFAOYSA-N 4-phenoxybenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1OC1=CC=CC=C1 MYPXYQMABPTFFN-UHFFFAOYSA-N 0.000 description 2
- ALBQXDHCMLLQMB-UHFFFAOYSA-N 4-phenylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=CC=C1 ALBQXDHCMLLQMB-UHFFFAOYSA-N 0.000 description 2
- ZQPOQWZJSQZACS-UHFFFAOYSA-N 5,6,7,8-tetrahydrophenanthrene-3-sulfonic acid Chemical compound C1CCCC2=C1C=CC1=CC=C(S(=O)(=O)O)C=C12 ZQPOQWZJSQZACS-UHFFFAOYSA-N 0.000 description 2
- GJJURAXVGOIXKG-UHFFFAOYSA-N 5-chloro-6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2C(Cl)=C(OC)C(OC)=CC2=C1 GJJURAXVGOIXKG-UHFFFAOYSA-N 0.000 description 2
- KBZDGTBCUVELGR-UHFFFAOYSA-N 5-chloro-6,7-dimethoxynaphthalene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2C(Cl)=C(OC)C(OC)=CC2=C1 KBZDGTBCUVELGR-UHFFFAOYSA-N 0.000 description 2
- GEQWITQJYWFQMK-UHFFFAOYSA-N 5-chloro-6-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=CC2=C(Cl)C(OC)=CC=C21 GEQWITQJYWFQMK-UHFFFAOYSA-N 0.000 description 2
- DKJVSIITPZVTRO-UHFFFAOYSA-N 6,7-dihydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(O)C(O)=CC2=C1 DKJVSIITPZVTRO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CSVSQXAZAHRPAJ-UHFFFAOYSA-N 6-phenylmethoxynaphthalene-2-sulfonic acid Chemical compound C1=CC2=CC(S(=O)(=O)O)=CC=C2C=C1OCC1=CC=CC=C1 CSVSQXAZAHRPAJ-UHFFFAOYSA-N 0.000 description 2
- BQTHNGZXYBVSFF-UHFFFAOYSA-N 6-phenylmethoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC2=CC(S(=O)(=O)Cl)=CC=C2C=C1OCC1=CC=CC=C1 BQTHNGZXYBVSFF-UHFFFAOYSA-N 0.000 description 2
- MBROCIXIVKLWLO-UHFFFAOYSA-N 7-ethoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(OCC)=CC=C21 MBROCIXIVKLWLO-UHFFFAOYSA-N 0.000 description 2
- JBXFALYHFAZOTL-UHFFFAOYSA-N 7-ethylnaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(CC)=CC=C21 JBXFALYHFAZOTL-UHFFFAOYSA-N 0.000 description 2
- GXYIEWUWNPMHFU-UHFFFAOYSA-N 7-ethylnaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(CC)=CC=C21 GXYIEWUWNPMHFU-UHFFFAOYSA-N 0.000 description 2
- DNCGBNFOSLTQQB-UHFFFAOYSA-N 7-methylnaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(C)=CC=C21 DNCGBNFOSLTQQB-UHFFFAOYSA-N 0.000 description 2
- GTIHXWGIIDMONZ-UHFFFAOYSA-N 7-methylnaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(C)=CC=C21 GTIHXWGIIDMONZ-UHFFFAOYSA-N 0.000 description 2
- QLYWHFRJMZDDTQ-UHFFFAOYSA-N 7-phenylmethoxynaphthalene-2-sulfonyl chloride Chemical compound C=1C2=CC(S(=O)(=O)Cl)=CC=C2C=CC=1OCC1=CC=CC=C1 QLYWHFRJMZDDTQ-UHFFFAOYSA-N 0.000 description 2
- PTOUQHXQKFKDDM-UHFFFAOYSA-N 8-chloro-7-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=C(Cl)C(OC)=CC=C21 PTOUQHXQKFKDDM-UHFFFAOYSA-N 0.000 description 2
- UDFCHANCMRCOQT-UHFFFAOYSA-N 9,10-dioxoanthracene-2-sulfonyl chloride Chemical compound C1=CC=C2C(=O)C3=CC(S(=O)(=O)Cl)=CC=C3C(=O)C2=C1 UDFCHANCMRCOQT-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- KKVAPKVCCVZAEQ-LTCKWSDVSA-N CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.COC1=CC=C(C=C(C=C2)S(O)(=O)=O)C2=C1.OC(C(F)(F)F)=O Chemical compound CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.COC1=CC=C(C=C(C=C2)S(O)(=O)=O)C2=C1.OC(C(F)(F)F)=O KKVAPKVCCVZAEQ-LTCKWSDVSA-N 0.000 description 2
- QKYRLPPVUYBJHP-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound COC=1C=C2C=CC(=CC2=CC1)S(=O)(=O)O.FC(C(=O)O)(F)F QKYRLPPVUYBJHP-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 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
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 241000562429 Jamides Species 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 206010047249 Venous thrombosis Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- SYGVMKIYGPBACY-UHFFFAOYSA-N benzyl n-(1-chloro-6-chlorosulfonylnaphthalen-2-yl)carbamate Chemical compound C1=CC2=CC(S(Cl)(=O)=O)=CC=C2C(Cl)=C1NC(=O)OCC1=CC=CC=C1 SYGVMKIYGPBACY-UHFFFAOYSA-N 0.000 description 2
- YKQXFRZYDCNBCV-UHFFFAOYSA-N benzyl n-(7-chlorosulfonylnaphthalen-2-yl)carbamate Chemical compound C=1C2=CC(S(=O)(=O)Cl)=CC=C2C=CC=1NC(=O)OCC1=CC=CC=C1 YKQXFRZYDCNBCV-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
- ULCKEERECJMLHP-UHFFFAOYSA-N dibenzofuran-2-sulfonyl chloride Chemical compound C1=CC=C2C3=CC(S(=O)(=O)Cl)=CC=C3OC2=C1 ULCKEERECJMLHP-UHFFFAOYSA-N 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- WHIDHHUCCTYJKA-UHFFFAOYSA-N isoquinoline-5-sulfonyl chloride Chemical compound N1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 WHIDHHUCCTYJKA-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- YFVJOHQIZCJFGM-UHFFFAOYSA-N methyl 2-[4-methanehydrazonoyl-2-[[3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]phenoxy]acetate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC(=O)COC1=CC=C(C=NN)C=C1CN1C(=O)C(NS(=O)(=O)C=2C=C3C=C(OC)C=CC3=CC=2)CC1 YFVJOHQIZCJFGM-UHFFFAOYSA-N 0.000 description 2
- DQCTULKVFJUBNA-QHCPKHFHSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-4-phenylbenzenesulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)CN1CC1=CC=CC(C#N)=C1 DQCTULKVFJUBNA-QHCPKHFHSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical group CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 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 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- PLUQFBYKHVFHMZ-UHFFFAOYSA-N quinoline-6-sulfonic acid Chemical compound N1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 PLUQFBYKHVFHMZ-UHFFFAOYSA-N 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- WUJACJDYYBJBCX-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=CC(C#N)=C1 WUJACJDYYBJBCX-AWEZNQCLSA-N 0.000 description 2
- ZFEBWMJKAXPDNZ-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[(4-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=C(C#N)C=C1 ZFEBWMJKAXPDNZ-AWEZNQCLSA-N 0.000 description 2
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
- HBUBRNBOYWHGHQ-UHFFFAOYSA-N tert-butyl-dimethyl-(3-methylphenoxy)silane Chemical compound CC1=CC=CC(O[Si](C)(C)C(C)(C)C)=C1 HBUBRNBOYWHGHQ-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 230000001732 thrombotic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- BPDOFCRUQGAMTG-UHFFFAOYSA-N trimethyl-(7-methylnaphthalen-2-yl)stannane Chemical compound C1=CC([Sn](C)(C)C)=CC2=CC(C)=CC=C21 BPDOFCRUQGAMTG-UHFFFAOYSA-N 0.000 description 2
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- APALRPYIDIBHQN-UHFFFAOYSA-N (1-phenylcyclopropyl)methanol Chemical compound C=1C=CC=CC=1C1(CO)CC1 APALRPYIDIBHQN-UHFFFAOYSA-N 0.000 description 1
- SOHLZANWVLCPHK-LBPRGKRZSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC(=O)OCC1=CC=CC=C1 SOHLZANWVLCPHK-LBPRGKRZSA-N 0.000 description 1
- FHOAKXBXYSJBGX-YFKPBYRVSA-N (2s)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CO)C(O)=O FHOAKXBXYSJBGX-YFKPBYRVSA-N 0.000 description 1
- RGXUCUWVGKLACF-UHFFFAOYSA-N (3-methylphenyl)methanamine Chemical compound CC1=CC=CC(CN)=C1 RGXUCUWVGKLACF-UHFFFAOYSA-N 0.000 description 1
- MGEKRXDJQFJADS-RXMQYKEDSA-N (3s)-2,2-diamino-3-methyl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound OC(=O)C(N)(N)[C@H](C)C(=O)OC(C)(C)C MGEKRXDJQFJADS-RXMQYKEDSA-N 0.000 description 1
- YNDAMDVOGKACTP-VKHMYHEASA-N (3s)-3-aminopyrrolidin-2-one Chemical compound N[C@H]1CCNC1=O YNDAMDVOGKACTP-VKHMYHEASA-N 0.000 description 1
- HMTSWYPNXFHGEP-UHFFFAOYSA-N (4-methylphenyl)methanamine Chemical compound CC1=CC=C(CN)C=C1 HMTSWYPNXFHGEP-UHFFFAOYSA-N 0.000 description 1
- BNINYSPPHGFMEY-UHFFFAOYSA-N (7-methoxynaphthalen-2-yl)-trimethylstannane Chemical compound C1=CC([Sn](C)(C)C)=CC2=CC(OC)=CC=C21 BNINYSPPHGFMEY-UHFFFAOYSA-N 0.000 description 1
- ONWRSBMOCIQLRK-VOTSOKGWSA-N (e)-2-phenylethenesulfonyl chloride Chemical compound ClS(=O)(=O)\C=C\C1=CC=CC=C1 ONWRSBMOCIQLRK-VOTSOKGWSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- HZKJAZKMSIAJRR-UHFFFAOYSA-N 1-(6-methoxypyridin-2-yl)cyclohexa-2,4-diene-1-sulfonic acid Chemical compound COC1=CC=CC(C2(C=CC=CC2)S(O)(=O)=O)=N1 HZKJAZKMSIAJRR-UHFFFAOYSA-N 0.000 description 1
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 1
- HXBMIQJOSHZCFX-UHFFFAOYSA-N 1-(bromomethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CBr HXBMIQJOSHZCFX-UHFFFAOYSA-N 0.000 description 1
- SCBZBMXPJYMXRC-UHFFFAOYSA-N 1-(bromomethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CBr)=C1 SCBZBMXPJYMXRC-UHFFFAOYSA-N 0.000 description 1
- ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
- FWLWTILKTABGKQ-UHFFFAOYSA-N 1-(bromomethyl)-3-methylbenzene Chemical compound CC1=CC=CC(CBr)=C1 FWLWTILKTABGKQ-UHFFFAOYSA-N 0.000 description 1
- LNWXALCHPJANMJ-UHFFFAOYSA-N 1-(bromomethyl)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(CBr)=C1 LNWXALCHPJANMJ-UHFFFAOYSA-N 0.000 description 1
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- UAWVMPOAIVZWFQ-UHFFFAOYSA-N 1-(chloromethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CCl UAWVMPOAIVZWFQ-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- VDIVGSUHQVOULM-UHFFFAOYSA-N 1-benzyl-2-chloromethylimidazole Chemical compound ClCC1=NC=CN1CC1=CC=CC=C1 VDIVGSUHQVOULM-UHFFFAOYSA-N 0.000 description 1
- XBOVMHAMNGXURZ-UHFFFAOYSA-N 1-bromo-2-(3-methylphenyl)benzene Chemical compound CC1=CC=CC(C=2C(=CC=CC=2)Br)=C1 XBOVMHAMNGXURZ-UHFFFAOYSA-N 0.000 description 1
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 description 1
- PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 1
- WJIFKOVZNJTSGO-UHFFFAOYSA-N 1-bromo-3-methylbenzene Chemical compound CC1=CC=CC(Br)=C1 WJIFKOVZNJTSGO-UHFFFAOYSA-N 0.000 description 1
- WXRCHIFZEUELKP-UHFFFAOYSA-N 1-bromo-4-(2-methylphenyl)benzene Chemical compound CC1=CC=CC=C1C1=CC=C(Br)C=C1 WXRCHIFZEUELKP-UHFFFAOYSA-N 0.000 description 1
- IMUPBLRBGMLYLB-UHFFFAOYSA-N 1-bromo-4-phenoxybenzene phenoxybenzene sulfuryl dichloride Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)Br.S(=O)(=O)(Cl)Cl.O(C1=CC=CC=C1)C1=CC=CC=C1 IMUPBLRBGMLYLB-UHFFFAOYSA-N 0.000 description 1
- PWJNDVAKQLOWRZ-UHFFFAOYSA-N 1-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC=C2C(O)=C(S(O)(=O)=O)C=CC2=C1 PWJNDVAKQLOWRZ-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical group CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- CVOZLMPXPDULSS-UHFFFAOYSA-N 1-phenoxycyclohexa-2,4-diene-1-sulfonic acid Chemical compound C=1C=CC=CC=1OC1(S(=O)(=O)O)CC=CC=C1 CVOZLMPXPDULSS-UHFFFAOYSA-N 0.000 description 1
- IBSUZZVWXUSKLV-UHFFFAOYSA-N 1-pyridin-3-ylcyclohexa-2,4-diene-1-sulfonic acid Chemical compound C=1C=CN=CC=1C1(S(=O)(=O)O)CC=CC=C1 IBSUZZVWXUSKLV-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
- FROLNLCCDLJCTP-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.OC(=O)C(O)C(O)C(O)=O FROLNLCCDLJCTP-UHFFFAOYSA-N 0.000 description 1
- GOPUHTXVZGIOHN-UHFFFAOYSA-N 2,4-dihydroxybenzohydrazide Chemical compound NNC(=O)C1=CC=C(O)C=C1O GOPUHTXVZGIOHN-UHFFFAOYSA-N 0.000 description 1
- AUCVZEYHEFAWHO-UHFFFAOYSA-N 2-(3-fluorophenyl)ethanamine Chemical compound NCCC1=CC=CC(F)=C1 AUCVZEYHEFAWHO-UHFFFAOYSA-N 0.000 description 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
- QIGHEIDADWLOKV-UHFFFAOYSA-N 2-(4-bromophenoxy)-3-chloropyridine Chemical compound ClC1=CC=CN=C1OC1=CC=C(Br)C=C1 QIGHEIDADWLOKV-UHFFFAOYSA-N 0.000 description 1
- QZOBOLDDGXPTBP-UHFFFAOYSA-N 2-(bromomethyl)thiophene Chemical compound BrCC1=CC=CS1 QZOBOLDDGXPTBP-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- WAFBTSBLIAENAA-UHFFFAOYSA-N 2-(pyridin-4-ylamino)ethanesulfonic acid Chemical compound OS(=O)(=O)CCNC1=CC=NC=C1 WAFBTSBLIAENAA-UHFFFAOYSA-N 0.000 description 1
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
- DCBBASNUFIWQRY-UHFFFAOYSA-N 2-[4-methanehydrazonoyl-2-[[3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]phenoxy]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)NC(C1=O)CCN1CC1=CC(C=NN)=CC=C1OCC(O)=O DCBBASNUFIWQRY-UHFFFAOYSA-N 0.000 description 1
- AVPPJLXWNOQEGV-YTTGMZPUSA-N 2-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-(2,3-dihydro-1h-inden-2-yl)acetamide Chemical compound C([C@@H](C1=O)N(CC(=O)NC2CC3=CC=CC=C3C2)S(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C#N)=C1 AVPPJLXWNOQEGV-YTTGMZPUSA-N 0.000 description 1
- KFTNWNYESKSFOM-HKBQPEDESA-N 2-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-[(4-methylphenyl)methyl]acetamide Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(C=CC=2)C#N)CC1)=O)CC(=O)NCC1=CC=C(C)C=C1 KFTNWNYESKSFOM-HKBQPEDESA-N 0.000 description 1
- NJMNFIPERDYOSY-YTTGMZPUSA-N 2-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-[2-(4-methylphenyl)ethyl]acetamide Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(C=CC=2)C#N)CC1)=O)CC(=O)NCCC1=CC=C(C)C=C1 NJMNFIPERDYOSY-YTTGMZPUSA-N 0.000 description 1
- HGXPMLGCWDDECY-VWLOTQADSA-N 2-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-ethylacetamide Chemical compound C([C@@H](C1=O)N(CC(=O)NCC)S(=O)(=O)C=2C=C3C=C(OC)C=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 HGXPMLGCWDDECY-VWLOTQADSA-N 0.000 description 1
- QCQRYNWXEMAYQI-PMERELPUSA-N 2-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-naphthalen-2-ylsulfonylamino]-n-(2-phenylethyl)acetamide Chemical compound C([C@@H](C1=O)N(CC(=O)NCCC=2C=CC=CC=2)S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 QCQRYNWXEMAYQI-PMERELPUSA-N 0.000 description 1
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 description 1
- WDRQIRQQLSDLCC-UHFFFAOYSA-N 2-bromo-2,3,3-trimethylbutanoic acid Chemical compound CC(C)(C)C(C)(Br)C(O)=O WDRQIRQQLSDLCC-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- VHCSBTPOPKFYIU-UHFFFAOYSA-N 2-chloroethanesulfonyl chloride Chemical compound ClCCS(Cl)(=O)=O VHCSBTPOPKFYIU-UHFFFAOYSA-N 0.000 description 1
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 description 1
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[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
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- ZHKGOAUOSDAZEK-UHFFFAOYSA-N 2-methoxyquinoline-7-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound COC1=NC2=CC(=CC=C2C=C1)S(=O)(=O)O.FC(C(=O)O)(F)F ZHKGOAUOSDAZEK-UHFFFAOYSA-N 0.000 description 1
- HFOLKLQITKXWPK-UHFFFAOYSA-N 2-methyl-7-(trifluoromethylsulfonyl)naphthalene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC2=CC(C)=CC=C21 HFOLKLQITKXWPK-UHFFFAOYSA-N 0.000 description 1
- AXIHPUHIJLFHFU-UHFFFAOYSA-N 2-methyl-7-(trifluoromethylsulfonyl)naphthalene trimethyl-(7-methylnaphthalen-2-yl)stannane Chemical compound CC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)C(F)(F)F.CC1=CC=C2C=CC(=CC2=C1)[Sn](C)(C)C AXIHPUHIJLFHFU-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- RIOSJKSGNLGONI-UHFFFAOYSA-N 2-phenylbenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 RIOSJKSGNLGONI-UHFFFAOYSA-N 0.000 description 1
- ZTJLYUVAFAMUKO-UHFFFAOYSA-N 2-phenylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CC=C1 ZTJLYUVAFAMUKO-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- MPJPPDINXOVGRK-UHFFFAOYSA-N 2h-pyridin-1-ylmethanamine Chemical compound NCN1CC=CC=C1 MPJPPDINXOVGRK-UHFFFAOYSA-N 0.000 description 1
- KHCXGFNZZRXOND-UHFFFAOYSA-N 3-(bromomethyl)pyridine Chemical compound BrCC1=CC=CN=C1 KHCXGFNZZRXOND-UHFFFAOYSA-N 0.000 description 1
- KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
- DGWXVKOHAAHEIH-UHFFFAOYSA-N 3-[(2-oxopyrrolidin-1-yl)methyl]benzonitrile Chemical compound O=C1CCCN1CC1=CC=CC(C#N)=C1 DGWXVKOHAAHEIH-UHFFFAOYSA-N 0.000 description 1
- VEGAVMCELTVUEI-JIDHJSLPSA-N 3-[[(3S)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]propanamide 2,2,2-trifluoroacetic acid Chemical compound C(#N)C=1C=C(CN2C([C@H](CC2)N(CCC(=O)N)S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=CC1.FC(C(=O)O)(F)F VEGAVMCELTVUEI-JIDHJSLPSA-N 0.000 description 1
- PSHKKVQYQIKXIF-LBPRGKRZSA-N 3-[[(3S)-3-(methylamino)-2-oxopyrrolidin-1-yl]methyl]benzonitrile Chemical compound O=C1[C@@H](NC)CCN1CC1=CC=CC(C#N)=C1 PSHKKVQYQIKXIF-LBPRGKRZSA-N 0.000 description 1
- OVYNLHFMQYWWCH-LTCKWSDVSA-N 3-[[(3S)-3-(methylamino)-2-oxopyrrolidin-1-yl]methyl]benzonitrile 1,2,3,4-tetrahydroisoquinoline-7-sulfonic acid 3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F.C1CNCC2=CC(S(=O)(=O)O)=CC=C21.O=C1[C@@H](NC)CCN1CC1=CC=CC(C#N)=C1 OVYNLHFMQYWWCH-LTCKWSDVSA-N 0.000 description 1
- XYRYXDKYLGCKKZ-YDALLXLXSA-N 3-[[(3S)-3-(methylamino)-2-oxopyrrolidin-1-yl]methyl]benzonitrile naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21.O=C1[C@@H](NC)CCN1CC1=CC=CC(C#N)=C1 XYRYXDKYLGCKKZ-YDALLXLXSA-N 0.000 description 1
- BWMPXGBHGZIGFJ-PPHPATTJSA-N 3-[[(3s)-3-amino-2,5-dioxopyrrolidin-1-yl]methyl]benzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CC(=O)N1CC1=CC=CC(C#N)=C1 BWMPXGBHGZIGFJ-PPHPATTJSA-N 0.000 description 1
- PGNJYAHAJXNPEK-PPHPATTJSA-N 3-[[(3s)-3-amino-2-oxoazetidin-1-yl]methyl]benzonitrile;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CN1CC1=CC=CC(C#N)=C1 PGNJYAHAJXNPEK-PPHPATTJSA-N 0.000 description 1
- RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- IHVNKSXTJZNBQA-UHFFFAOYSA-N 3-methyl-4-nitrobenzonitrile Chemical compound CC1=CC(C#N)=CC=C1[N+]([O-])=O IHVNKSXTJZNBQA-UHFFFAOYSA-N 0.000 description 1
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 1
- IDJWDPIOJWRCGY-UHFFFAOYSA-N 4,5-dichlorothiophene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound ClC=1C=C(SC1Cl)S(=O)(=O)O.FC(C(=O)O)(F)F IDJWDPIOJWRCGY-UHFFFAOYSA-N 0.000 description 1
- IVTWLTRKVRJPNG-UHFFFAOYSA-N 4,5-dichlorothiophene-2-sulfonyl chloride Chemical compound ClC=1C=C(S(Cl)(=O)=O)SC=1Cl IVTWLTRKVRJPNG-UHFFFAOYSA-N 0.000 description 1
- JDAQHEXNULKNCY-UHFFFAOYSA-N 4-(2-methoxyphenyl)benzenesulfonyl chloride Chemical compound COC1=CC=CC=C1C1=CC=C(S(Cl)(=O)=O)C=C1 JDAQHEXNULKNCY-UHFFFAOYSA-N 0.000 description 1
- DFYOEMIZUXRAQV-UHFFFAOYSA-N 4-(3-chloropyridin-2-yl)oxybenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1OC1=NC=CC=C1Cl DFYOEMIZUXRAQV-UHFFFAOYSA-N 0.000 description 1
- OHVJVSGIYVAZFD-UHFFFAOYSA-N 4-(3-methylphenyl)benzenesulfonyl chloride Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)S(Cl)(=O)=O)=C1 OHVJVSGIYVAZFD-UHFFFAOYSA-N 0.000 description 1
- HIZANHXITWHUAH-UHFFFAOYSA-N 4-(4-bromophenyl)pyridine;4-bromopyridine;hydrochloride Chemical compound Cl.BrC1=CC=NC=C1.C1=CC(Br)=CC=C1C1=CC=NC=C1 HIZANHXITWHUAH-UHFFFAOYSA-N 0.000 description 1
- VZTUOMVKSXENCG-UHFFFAOYSA-N 4-(benzhydrylideneamino)-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1N=C(C=1C=CC=CC=1)C1=CC=CC=C1 VZTUOMVKSXENCG-UHFFFAOYSA-N 0.000 description 1
- WZIYCIBURCPKAR-UHFFFAOYSA-N 4-(chloromethyl)pyridine Chemical compound ClCC1=CC=NC=C1 WZIYCIBURCPKAR-UHFFFAOYSA-N 0.000 description 1
- IEAQVVBZJPEDJY-NTISSMGPSA-N 4-[[(3S)-3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylmethylamino]-2-oxopyrrolidin-1-yl]methyl]pyridine-2-carboximidamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NCS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CC=NC(C(N)=N)=C1 IEAQVVBZJPEDJY-NTISSMGPSA-N 0.000 description 1
- OMECHTUZMYEMGX-LMOVPXPDSA-N 4-[[(3S)-3-[(6-amino-5-chloronaphthalen-2-yl)sulfonylmethylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.NC=1C(=C2C=CC(=CC2=CC1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC=1C=C(SC1)C(=N)N)=O)Cl OMECHTUZMYEMGX-LMOVPXPDSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- NSPBHXHCHBEESU-BOXHHOBZSA-N 4-[[(3s)-3-[benzyl-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]amino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC1=CC=CC=C1 NSPBHXHCHBEESU-BOXHHOBZSA-N 0.000 description 1
- HCRUAUPANSKASS-FTBISJDPSA-N 4-amino-3-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonyl-methylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)N(C)S(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C(N)=N)=CC=C1N HCRUAUPANSKASS-FTBISJDPSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- HTRNHWBOBYFTQF-UHFFFAOYSA-N 4-bromo-2-fluoro-1-phenylbenzene Chemical group FC1=CC(Br)=CC=C1C1=CC=CC=C1 HTRNHWBOBYFTQF-UHFFFAOYSA-N 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- CTEWUQNEQPLMMJ-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-2-sulfonic acid Chemical compound C1CCCC2=CC(S(=O)(=O)O)=CC=C21 CTEWUQNEQPLMMJ-UHFFFAOYSA-N 0.000 description 1
- QPSBKIYIBNRHFC-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CCCC2=CC(S(=O)(=O)O)=CC=C21 QPSBKIYIBNRHFC-UHFFFAOYSA-N 0.000 description 1
- FNEIMPFRVQQOMV-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-2-sulfonyl chloride Chemical compound C1CCCC2=CC(S(=O)(=O)Cl)=CC=C21 FNEIMPFRVQQOMV-UHFFFAOYSA-N 0.000 description 1
- ZKLCJLHYZXQTTA-UHFFFAOYSA-N 5,6,7,8-tetrahydrophenanthrene-3-sulfonyl chloride Chemical compound C1CCCC2=C1C=CC1=CC=C(S(=O)(=O)Cl)C=C12 ZKLCJLHYZXQTTA-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- KCISEPFGNAALSA-UHFFFAOYSA-N 5-chloro-6-(phenylmethoxycarbonylamino)naphthalene-2-sulfonic acid Chemical compound C1=CC2=CC(S(=O)(=O)O)=CC=C2C(Cl)=C1NC(=O)OCC1=CC=CC=C1 KCISEPFGNAALSA-UHFFFAOYSA-N 0.000 description 1
- ZHFZUAWTDJGTTL-SFHVURJKSA-N 5-chloro-n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)CN1CC1=CC=CC(C#N)=C1 ZHFZUAWTDJGTTL-SFHVURJKSA-N 0.000 description 1
- SORSTNOXGOXWAO-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)S1 SORSTNOXGOXWAO-UHFFFAOYSA-N 0.000 description 1
- JURWPUACOPQKGW-UHFFFAOYSA-N 5-phenylpentanamide Chemical compound NC(=O)CCCCC1=CC=CC=C1 JURWPUACOPQKGW-UHFFFAOYSA-N 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
- IMSZMAMIAUKQMV-UHFFFAOYSA-N 6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(OC)C(OC)=CC2=C1 IMSZMAMIAUKQMV-UHFFFAOYSA-N 0.000 description 1
- WTUCGFYIXJREBR-UHFFFAOYSA-N 6,7-dimethoxynaphthalene-2-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2C=C(OC)C(OC)=CC2=C1 WTUCGFYIXJREBR-UHFFFAOYSA-N 0.000 description 1
- URNCEBDXFPRJCI-UHFFFAOYSA-N 6-(phenylmethoxycarbonylamino)naphthalene-2-sulfonic acid Chemical compound C1=CC2=CC(S(=O)(=O)O)=CC=C2C=C1NC(=O)OCC1=CC=CC=C1 URNCEBDXFPRJCI-UHFFFAOYSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- IFIHYLCUKYCKRH-UHFFFAOYSA-N 6-bromoquinoline Chemical compound N1=CC=CC2=CC(Br)=CC=C21 IFIHYLCUKYCKRH-UHFFFAOYSA-N 0.000 description 1
- HKOGBLBUENUGKY-YDALLXLXSA-N 6-methoxynaphthalene-2-sulfonic acid 3-[[(3S)-3-(methylamino)-2-oxopyrrolidin-1-yl]methyl]benzonitrile Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(OC)=CC=C21.O=C1[C@@H](NC)CCN1CC1=CC=CC(C#N)=C1 HKOGBLBUENUGKY-YDALLXLXSA-N 0.000 description 1
- LRYLPTQMSIXZGZ-UHFFFAOYSA-N 7-(methylamino)naphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(NC)=CC=C21 LRYLPTQMSIXZGZ-UHFFFAOYSA-N 0.000 description 1
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 1
- IMHFRXKNAIQMBZ-UHFFFAOYSA-N 7-bromo-2-methoxyquinoline 2-methoxyquinoline-7-sulfonyl chloride Chemical compound BrC1=CC=C2C=CC(=NC2=C1)OC.COC1=NC2=CC(=CC=C2C=C1)S(=O)(=O)Cl IMHFRXKNAIQMBZ-UHFFFAOYSA-N 0.000 description 1
- UNFNRIIETORURP-UHFFFAOYSA-N 7-methoxynaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(OC)=CC=C21 UNFNRIIETORURP-UHFFFAOYSA-N 0.000 description 1
- IXJVEDCMKWGSDI-YDALLXLXSA-N 7-methoxynaphthalene-2-sulfonic acid 3-[[(3S)-3-(methylamino)-2-oxopyrrolidin-1-yl]methyl]benzonitrile Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OC)=CC=C21.O=C1[C@@H](NC)CCN1CC1=CC=CC(C#N)=C1 IXJVEDCMKWGSDI-YDALLXLXSA-N 0.000 description 1
- TUBMBNKCTWXIDO-UHFFFAOYSA-N 7-phenylmethoxynaphthalene-2-sulfonic acid Chemical compound C=1C2=CC(S(=O)(=O)O)=CC=C2C=CC=1OCC1=CC=CC=C1 TUBMBNKCTWXIDO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- MMNWSHJJPDXKCH-UHFFFAOYSA-N 9,10-dioxoanthracene-2-sulfonic acid Chemical compound C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 MMNWSHJJPDXKCH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- LEYUSBMPNDKLMJ-UHFFFAOYSA-N BrC=1C=NC=CC1.N1=CC(=CC=C1)C1=CC=C(C=C1)Br Chemical compound BrC=1C=NC=CC1.N1=CC(=CC=C1)C1=CC=C(C=C1)Br LEYUSBMPNDKLMJ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VJEJSYCSJNYCFV-FTBISJDPSA-N C(#N)C1=CC=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=C1.FC(C(=O)O)(F)F Chemical compound C(#N)C1=CC=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)=O)C=C1.FC(C(=O)O)(F)F VJEJSYCSJNYCFV-FTBISJDPSA-N 0.000 description 1
- KGYOPFHDAMGLNL-JMAPEOGHSA-N C(#N)C=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)[N+](=O)[O-])=O)C=CC1.FC(C(=O)O)(F)F Chemical compound C(#N)C=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC=C(C=C2)[N+](=O)[O-])=O)C=CC1.FC(C(=O)O)(F)F KGYOPFHDAMGLNL-JMAPEOGHSA-N 0.000 description 1
- XFPGBWVZEWLUJJ-ZOWNYOTGSA-N C(#N)C=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C=2SC(=C(C2)Cl)Cl)=O)C=CC1.FC(C(=O)O)(F)F Chemical compound C(#N)C=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C=2SC(=C(C2)Cl)Cl)=O)C=CC1.FC(C(=O)O)(F)F XFPGBWVZEWLUJJ-ZOWNYOTGSA-N 0.000 description 1
- FFSZFXOHEILWBE-IXSARBFQSA-N C(=O)(OC(C)(C)C)N1CC(CC1)N.C(=O)(OC(C)(C)C)N1C[C@H](CC1)N.C1=C(C=CC2=CC=CC=C12)S(=O)(=O)O Chemical compound C(=O)(OC(C)(C)C)N1CC(CC1)N.C(=O)(OC(C)(C)C)N1C[C@H](CC1)N.C1=C(C=CC2=CC=CC=C12)S(=O)(=O)O FFSZFXOHEILWBE-IXSARBFQSA-N 0.000 description 1
- LJMNSJABKBSAKU-UHFFFAOYSA-N C1=C(C=CC=2OC3=C(C21)C=CC=C3)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound C1=C(C=CC=2OC3=C(C21)C=CC=C3)S(=O)(=O)O.FC(C(=O)O)(F)F LJMNSJABKBSAKU-UHFFFAOYSA-N 0.000 description 1
- JGLQNAVYNHELIC-UHFFFAOYSA-N CC1=CC=C2C=CC(=CC2=C1)O.CC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)C(F)(F)F Chemical compound CC1=CC=C2C=CC(=CC2=C1)O.CC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)C(F)(F)F JGLQNAVYNHELIC-UHFFFAOYSA-N 0.000 description 1
- XZITWMGRCIRGSA-UHFFFAOYSA-N CC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound CC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F XZITWMGRCIRGSA-UHFFFAOYSA-N 0.000 description 1
- WIOKCKSFXZUPKG-LTCKWSDVSA-N CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O Chemical compound CN[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O WIOKCKSFXZUPKG-LTCKWSDVSA-N 0.000 description 1
- JPIYIGCKYFRTKD-UHFFFAOYSA-N COC1=CC2=CC(=CC=C2C=C1)S(=O)(=O)C(F)(F)F.COC1=CC2=CC(=CC=C2C=C1)C Chemical compound COC1=CC2=CC(=CC=C2C=C1)S(=O)(=O)C(F)(F)F.COC1=CC2=CC(=CC=C2C=C1)C JPIYIGCKYFRTKD-UHFFFAOYSA-N 0.000 description 1
- DBEATAZEVCPKQW-UHFFFAOYSA-N COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F DBEATAZEVCPKQW-UHFFFAOYSA-N 0.000 description 1
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
- JQTRAGLJAVGGLT-MERQFXBCSA-N Cl.N[C@@H]1C(N(CC1)CC1=C(C#N)C=CC=C1)=O Chemical compound Cl.N[C@@H]1C(N(CC1)CC1=C(C#N)C=CC=C1)=O JQTRAGLJAVGGLT-MERQFXBCSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- DBCHVUVYOXRECR-IKXQUJFKSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC=C(C=C2)C=2C=NC=CC2)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC=C(C=C2)C=2C=NC=CC2)=O)C=CC1 DBCHVUVYOXRECR-IKXQUJFKSA-N 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- 241000282412 Homo Species 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
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- YGRFXPCHZBRUKP-UHFFFAOYSA-N Methoxamine hydrochloride Chemical compound Cl.COC1=CC=C(OC)C(C(O)C(C)N)=C1 YGRFXPCHZBRUKP-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- QVBKSRCAAVGQQF-LJAQVGFWSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-N-[(3-nitrophenyl)methyl]naphthalene-2-sulfonamide Chemical compound NN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC(=CC=C3C=C2)OC)CC2=CC(=CC=C2)[N+](=O)[O-])=O)C=CC1 QVBKSRCAAVGQQF-LJAQVGFWSA-N 0.000 description 1
- KAJAARFVLSWAOW-BQAIUKQQSA-N N-[(3S)-1-[[3-[(hydroxyhydrazinylidene)methyl]phenyl]methyl]-2-oxopyrrolidin-3-yl]-6-methoxy-N-methylnaphthalene-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.ONN=CC=1C=C(CN2C([C@H](CC2)N(S(=O)(=O)C2=CC3=CC=C(C=C3C=C2)OC)C)=O)C=CC1 KAJAARFVLSWAOW-BQAIUKQQSA-N 0.000 description 1
- FFPGKOVGAWVFKD-UHFFFAOYSA-N NCC1=CSC=C1.OC(C(F)(F)F)=O Chemical compound NCC1=CSC=C1.OC(C(F)(F)F)=O FFPGKOVGAWVFKD-UHFFFAOYSA-N 0.000 description 1
- OVBDHXGBHMISNL-UHFFFAOYSA-N NN=CC=1C=C(CN2C(CCC2)=O)C=CC1 Chemical compound NN=CC=1C=C(CN2C(CCC2)=O)C=CC1 OVBDHXGBHMISNL-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- YLFNODYYOXOFJO-IDMXKUIJSA-N N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O Chemical compound N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O YLFNODYYOXOFJO-IDMXKUIJSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GWDCVMIEISJHES-FTBISJDPSA-N OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)OC)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)OC)CN1CC1=CC=CC(C=NN)=C1 GWDCVMIEISJHES-FTBISJDPSA-N 0.000 description 1
- NKBSYLJRVLPKJV-VZYDHVRKSA-N OC(=O)C(F)(F)F.C([C@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C=NN)=C1 Chemical compound OC(=O)C(F)(F)F.C([C@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=CC(C=NN)=C1 NKBSYLJRVLPKJV-VZYDHVRKSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- DIEDRUHXKKTURK-REOHCLBHSA-N [(3s)-2-oxoazetidin-3-yl]carbamic acid Chemical compound OC(=O)N[C@H]1CNC1=O DIEDRUHXKKTURK-REOHCLBHSA-N 0.000 description 1
- YOVQJEYSSSBKFO-UHFFFAOYSA-N [Br-].CC=1C=CN[NH+]=1 Chemical compound [Br-].CC=1C=CN[NH+]=1 YOVQJEYSSSBKFO-UHFFFAOYSA-N 0.000 description 1
- LDKMLHJERAMUOG-UHFFFAOYSA-N [O-][N+]1=CC(=CC=C1)C1(CC=CC=C1)S(=O)(=O)O.FC(C(=O)O)(F)F Chemical compound [O-][N+]1=CC(=CC=C1)C1(CC=CC=C1)S(=O)(=O)O.FC(C(=O)O)(F)F LDKMLHJERAMUOG-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- PAAZCQANMCYGAW-UHFFFAOYSA-N acetic acid;2,2,2-trifluoroacetic acid Chemical compound CC(O)=O.OC(=O)C(F)(F)F PAAZCQANMCYGAW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- QBBJFYQPYXKIEB-UHFFFAOYSA-N benzonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N#CC1=CC=CC=C1 QBBJFYQPYXKIEB-UHFFFAOYSA-N 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- KLFNVPJUJPGMNW-UHFFFAOYSA-N benzyl n-(7-chlorosulfonylnaphthalen-2-yl)-n-methylcarbamate Chemical compound C=1C=C2C=CC(S(Cl)(=O)=O)=CC2=CC=1N(C)C(=O)OCC1=CC=CC=C1 KLFNVPJUJPGMNW-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 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
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000010779 crude oil Substances 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
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000012067 demethylated product Substances 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-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
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical group Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 229940114119 gentisate Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 description 1
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- XSWLEPPMXHFGFT-UHFFFAOYSA-N hex-5-ene-3-sulfonic acid Chemical compound CCC(S(O)(=O)=O)CC=C XSWLEPPMXHFGFT-UHFFFAOYSA-N 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical group N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 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
- RPHFGEHBXPSYLK-UHFFFAOYSA-N methanamine;dihydrochloride Chemical compound Cl.Cl.NC RPHFGEHBXPSYLK-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229960004269 methoxamine hydrochloride Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- WOHRWNVELIPMGN-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2,5-dioxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)C(=O)N1CC1=CC=CC(C#N)=C1 WOHRWNVELIPMGN-NRFANRHFSA-N 0.000 description 1
- PWOLXFQSKBBJIM-DEOSSOPVSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxoazepan-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CCCN1CC1=CC=CC(C#N)=C1 PWOLXFQSKBBJIM-DEOSSOPVSA-N 0.000 description 1
- UEBOWLOYLYTZOI-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxoazetidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)N1CC1=CC=CC(C#N)=C1 UEBOWLOYLYTZOI-NRFANRHFSA-N 0.000 description 1
- FEXQLWBBSQJSJA-BDQAORGHSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide;3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=C3CNCCC3=CC=2)CN1CC1=CC=CC(C#N)=C1 FEXQLWBBSQJSJA-BDQAORGHSA-N 0.000 description 1
- HPKREPFLPLOZAJ-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-2-methyl-3,4-dihydro-1h-isoquinoline-7-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC=C3CCN(CC3=C2)C)CN1CC1=CC=CC(C#N)=C1 HPKREPFLPLOZAJ-NRFANRHFSA-N 0.000 description 1
- COWBXUAFYNWONZ-SFHVURJKSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-2-ylthiophene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2SC(=CC=2)C=2N=CC=CC=2)CN1CC1=CC=CC(C#N)=C1 COWBXUAFYNWONZ-SFHVURJKSA-N 0.000 description 1
- LZZBSAOYIGQPRQ-NDEPHWFRSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-7-phenylmethoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=C(OCC=4C=CC=CC=4)C=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 LZZBSAOYIGQPRQ-NDEPHWFRSA-N 0.000 description 1
- VZVDXIFQKAZFGJ-FQEVSTJZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]benzo[f][1,3]benzodioxole-6-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=C4OCOC4=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 VZVDXIFQKAZFGJ-FQEVSTJZSA-N 0.000 description 1
- LJIKZQPVEMNVJF-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]dibenzofuran-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C4=CC=CC=C4OC3=CC=2)CN1CC1=CC=CC(C#N)=C1 LJIKZQPVEMNVJF-NRFANRHFSA-N 0.000 description 1
- OYTTYLWOCYNYLM-IBGZPJMESA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]isoquinoline-5-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C3=CC=NC=C3C=CC=2)CN1CC1=CC=CC(C#N)=C1 OYTTYLWOCYNYLM-IBGZPJMESA-N 0.000 description 1
- MUKIGOMZHGXNRK-FQEVSTJZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-1-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C3=CC=CC=C3C=CC=2)CN1CC1=CC=CC(C#N)=C1 MUKIGOMZHGXNRK-FQEVSTJZSA-N 0.000 description 1
- TZRDBGOIVNEENX-FQEVSTJZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]quinoline-6-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=CC=NC3=CC=2)CN1CC1=CC=CC(C#N)=C1 TZRDBGOIVNEENX-FQEVSTJZSA-N 0.000 description 1
- GNHUCPDGBMXOIM-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C([C@@H](C1)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 GNHUCPDGBMXOIM-NRFANRHFSA-N 0.000 description 1
- WGGXDVHYCNATBJ-NRFANRHFSA-N n-[(3s)-1-[(4-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CC=C(C#N)C=C1 WGGXDVHYCNATBJ-NRFANRHFSA-N 0.000 description 1
- NIYCWDHSWVJIKD-ZOWNYOTGSA-N n-[(3s)-pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N[C@H]1CCNC1 NIYCWDHSWVJIKD-ZOWNYOTGSA-N 0.000 description 1
- MGECWACBPMUSOO-UHFFFAOYSA-N n-[1-[(3-cyanophenyl)methyl]-2-oxopiperidin-3-yl]naphthalene-2-sulfonamide Chemical compound O=C1C(NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CCCN1CC1=CC=CC(C#N)=C1 MGECWACBPMUSOO-UHFFFAOYSA-N 0.000 description 1
- KVUMTOFGJNTJNN-UHFFFAOYSA-N n-[1-[(3-cyanophenyl)methyl]-5-oxopyrrolidin-3-yl]dibenzofuran-2-sulfonamide Chemical compound O=C1CC(NS(=O)(=O)C=2C=C3C4=CC=CC=C4OC3=CC=2)CN1CC1=CC=CC(C#N)=C1 KVUMTOFGJNTJNN-UHFFFAOYSA-N 0.000 description 1
- OOXFGQNCCMTCSO-LMOVPXPDSA-N n-benzyl-2-[[(3s)-1-[(5-carbamimidoylthiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-(4,5-dichlorothiophen-2-yl)sulfonylamino]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC(=O)NCC=3C=CC=CC=3)S(=O)(=O)C=3SC(Cl)=C(Cl)C=3)CC2)=O)=C1 OOXFGQNCCMTCSO-LMOVPXPDSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- JNHZPXFARRJZQR-UHFFFAOYSA-N n-ethylpyridin-3-amine Chemical compound CCNC1=CC=CN=C1 JNHZPXFARRJZQR-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XBCAHQUVHHVHHL-UHFFFAOYSA-N naphthalen-2-ylmethanamine Chemical compound C1=CC=CC2=CC(CN)=CC=C21 XBCAHQUVHHVHHL-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
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- RYUQZMGIWVNPPE-UHFFFAOYSA-N phenylmethanamine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCC1=CC=CC=C1 RYUQZMGIWVNPPE-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
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- FOWPHZWPFDBTAY-UHFFFAOYSA-N pyrrolidin-3-amine;2,2,2-trifluoroacetic acid Chemical compound NC1CCNC1.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F FOWPHZWPFDBTAY-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- XELRMPRLCPFTBH-UHFFFAOYSA-N quinazoline-2,4-diamine Chemical compound C1=CC=CC2=NC(N)=NC(N)=C21 XELRMPRLCPFTBH-UHFFFAOYSA-N 0.000 description 1
- AUDKCUOUBLCZQR-UHFFFAOYSA-N quinoline-6-sulfonyl chloride Chemical compound N1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 AUDKCUOUBLCZQR-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- JFXDYPLHFRYDJD-UHFFFAOYSA-M sodium;6,7-dihydroxynaphthalene-2-sulfonate Chemical compound [Na+].C1=C(S([O-])(=O)=O)C=C2C=C(O)C(O)=CC2=C1 JFXDYPLHFRYDJD-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- QPUVKJBPFFRLRR-ZLTKDMPESA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate;naphthalene-2-sulfonic acid Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1.C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 QPUVKJBPFFRLRR-ZLTKDMPESA-N 0.000 description 1
- NXWNLOCSIIRTNL-INIZCTEOSA-N tert-butyl n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxoazepan-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCCCN1CC1=CC=CC(C#N)=C1 NXWNLOCSIIRTNL-INIZCTEOSA-N 0.000 description 1
- MQSNSCMXWVADDJ-ZDUSSCGKSA-N tert-butyl n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxoazetidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CN1CC1=CC=CC(C#N)=C1 MQSNSCMXWVADDJ-ZDUSSCGKSA-N 0.000 description 1
- DVWCHAUBYVZILO-LURJTMIESA-N tert-butyl n-[(3s)-2-oxopyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1=O DVWCHAUBYVZILO-LURJTMIESA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- NLJDBTZLVTWXRG-UHFFFAOYSA-N tert-butylazanium;iodide Chemical compound [I-].CC(C)(C)[NH3+] NLJDBTZLVTWXRG-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/416—2,5-Pyrrolidine-diones 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 other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/481,024 US5612353A (en) | 1995-06-07 | 1995-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
| PCT/US1996/009816 WO1996040679A1 (en) | 1995-06-07 | 1996-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) n-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI9620093A true SI9620093A (sl) | 1999-02-28 |
Family
ID=23910281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9620093A SI9620093A (sl) | 1995-06-07 | 1996-06-07 | Substituirane (sulfinska kislina, sulfonska kislina, sulfonilamino ali sulfinilamino) N-/(aminoiminometil)fenilalkil/-azaheterociklilamidne spojine |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5612353A (enExample) |
| EP (1) | EP0853618B1 (enExample) |
| JP (1) | JP4312829B2 (enExample) |
| KR (1) | KR100291711B1 (enExample) |
| CN (1) | CN1190395A (enExample) |
| AP (1) | AP799A (enExample) |
| AT (1) | ATE520655T1 (enExample) |
| AU (1) | AU714319B2 (enExample) |
| BG (1) | BG63628B1 (enExample) |
| BR (1) | BR9608405A (enExample) |
| CA (1) | CA2223403C (enExample) |
| CZ (1) | CZ385397A3 (enExample) |
| EA (1) | EA000700B1 (enExample) |
| HU (1) | HUP9801882A3 (enExample) |
| MX (1) | MX9709977A (enExample) |
| NO (1) | NO310457B1 (enExample) |
| OA (1) | OA10752A (enExample) |
| PL (1) | PL323780A1 (enExample) |
| SI (1) | SI9620093A (enExample) |
| SK (1) | SK160697A3 (enExample) |
| WO (1) | WO1996040679A1 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6034093A (en) * | 1995-06-07 | 2000-03-07 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
| US5731315A (en) * | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
| US5958918A (en) * | 1995-06-07 | 1999-09-28 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N- (aminominomethyl)phenylalkyl!-azaheterocyclylamide compounds |
| US6080767A (en) * | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US6057342A (en) * | 1996-08-16 | 2000-05-02 | Dupont Pharmaceutical Co. | Amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof |
| CN1244798A (zh) * | 1996-12-13 | 2000-02-16 | 罗纳·布朗克罗尔药制品有限公司 | 磺酸或磺酰氨基n-(杂芳烷基)-氮杂环酰胺化合物 |
| US6602864B1 (en) * | 1996-12-13 | 2003-08-05 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
| EP0986551B1 (en) | 1997-05-30 | 2006-08-02 | Takeda Pharmaceutical Company Limited | Sulfonamide derivatives, their production and use |
| ZA985247B (en) * | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| DE69833036T2 (de) | 1997-09-30 | 2006-06-22 | Daiichi Pharmaceutical Co., Ltd. | Sulfonylderivate |
| US6271237B1 (en) | 1997-12-22 | 2001-08-07 | Dupont Pharmaceuticals Company | Nitrogen containing heteromatics with ortho-substituted P1s as factor Xa inhabitors |
| CA2314401A1 (en) * | 1997-12-22 | 1999-07-01 | Du Pont Pharmaceuticals Company | Nitrogen containing heteroaromatics with ortho-substituted p1's as factor xa inhibitors |
| UA59433C2 (uk) * | 1998-01-27 | 2003-09-15 | Авентіс Фармасьютікалс Продактс Інк. | ЗАМІЩЕНІ ОКСОАЗАГЕТЕРОЦИКЛІЧНІ ІНГІБІТОРИ ФАКТОРА Хa ТА ПРОМІЖНІ СПОЛУКИ ДЛЯ ЇХ ОТРИМАННЯ |
| 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 |
| US6291514B1 (en) | 1998-02-09 | 2001-09-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors |
| WO1999040088A1 (en) * | 1998-02-09 | 1999-08-12 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines as protease inhibitors, in particular as urokinase inhibitors |
| AU5196399A (en) * | 1998-08-11 | 2000-03-06 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
| DE19839499A1 (de) * | 1998-08-29 | 2000-03-02 | Merck Patent Gmbh | 2-Oxo-2H-chinolinderivate |
| WO2000032590A1 (en) * | 1998-11-25 | 2000-06-08 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
| EP1150979A1 (en) * | 1999-02-09 | 2001-11-07 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines as protease inhibitors |
| DE19909237A1 (de) * | 1999-03-03 | 2000-09-07 | Merck Patent Gmbh | Pyrazol-3-on-derivate |
| US6794412B1 (en) * | 1999-03-11 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Treatment of thrombosis by combined use of a factor Xa inhibitor and aspirin |
| US6586617B1 (en) * | 1999-04-28 | 2003-07-01 | Sumitomo Chemical Takeda Agro Company, Limited | Sulfonamide derivatives |
| JP2001026506A (ja) * | 1999-04-28 | 2001-01-30 | Takeda Chem Ind Ltd | スルホンアミド誘導体 |
| AU5566300A (en) | 1999-06-22 | 2001-01-09 | Takeda Chemical Industries Ltd. | Acylhydrazine derivatives, process for preparing the same and use thereof |
| EP1208097B1 (en) * | 1999-07-28 | 2009-02-18 | Aventis Pharmaceuticals Inc. | Substituted oxoazaheterocyclyl compounds |
| US6544981B2 (en) | 2000-06-09 | 2003-04-08 | Bristol-Myers Squibb Company | Lactam inhibitors of factor Xa and method |
| US6511973B2 (en) | 2000-08-02 | 2003-01-28 | Bristol-Myers Squibb Co. | Lactam inhibitors of FXa and method |
| EP1317429B1 (en) | 2000-09-11 | 2006-08-30 | Genentech Inc. | Amidine inhibitors of serine proteases |
| AU2002214266A1 (en) * | 2000-11-08 | 2002-05-21 | Takeda Chemical Industries Ltd. | Carbamate derivatives, process for producing the same and use thereof |
| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| AR032230A1 (es) * | 2001-01-16 | 2003-10-29 | Sumitomo Chem Takeda Agro Co | Derivado sulfonamida conteniendo una composicion agricola y horticola |
| ES2274013T3 (es) | 2001-01-26 | 2007-05-16 | Schering Corporation | Combinaciones de activador(es) del receptor activado por el proliferador de los peroxisomas (ppar) e inhibidor(es)m de la absorcion de estelores y tratamientos para trastornos vasculares. |
| US20060287254A1 (en) * | 2001-01-26 | 2006-12-21 | Schering Corporation | Use of substituted azetidinone compounds for the treatment of sitosterolemia |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| CA2434430A1 (en) | 2001-01-26 | 2002-08-01 | Harry R. Davis | The use of substituted azetidinone compounds for the treatment of sitosterolemia |
| WO2002060894A2 (en) | 2001-01-30 | 2002-08-08 | Bristol-Myers Squibb Company | Sulfonamide lactam inhibitors of factor xa |
| US6710061B2 (en) | 2001-03-09 | 2004-03-23 | Ortho-Mcneil Pharamceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
| CA2440389A1 (en) | 2001-03-09 | 2002-10-03 | Ortho-Mcneil Pharmaceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
| DE10112768A1 (de) * | 2001-03-16 | 2002-09-19 | Merck Patent Gmbh | Phenylderivate 3 |
| DE10139060A1 (de) | 2001-08-08 | 2003-02-20 | Merck Patent Gmbh | Phenylderivate |
| AU2002336609B2 (en) | 2001-09-21 | 2006-08-24 | Merck Sharp & Dohme Corp. | Treatment of xanthoma with azetidinone derivatives as sterol absorption inhibitors |
| US7053080B2 (en) | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
| DE10239821A1 (de) | 2002-08-29 | 2004-03-11 | Roche Diagnostics Gmbh | Verbesserung der Spezifität bei der Bestimmung von Antithrombin |
| WO2004043457A1 (en) | 2002-11-06 | 2004-05-27 | Schering Corporation | Cholesterol absorptions inhibitors for the treatment of autoimmune disorders |
| EP1564213A4 (en) | 2002-11-22 | 2009-05-27 | Takeda Pharmaceutical | IMIDAZOLE DERIVATIVE, METHOD FOR THE PRODUCTION AND USE THEREOF |
| PT1569912E (pt) | 2002-12-03 | 2015-09-15 | Pharmacyclics Llc | Derivados 2-(2-hidroxibifenil-3-il)-1h-benzoimidazole-5- carboxamidina como inibidores do fator viia |
| DE10302500A1 (de) | 2003-01-23 | 2004-07-29 | Merck Patent Gmbh | Carbonsäureamidderivate |
| CN1756756A (zh) * | 2003-03-07 | 2006-04-05 | 先灵公司 | 取代的2-吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途 |
| US7459442B2 (en) * | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| WO2004081004A1 (en) | 2003-03-07 | 2004-09-23 | Schering Corporation | Substituted azetidinone compounds, formulations and uses thereof for the treatment of hypercholesterolemia |
| US7235543B2 (en) | 2003-03-07 | 2007-06-26 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| AU2004249671A1 (en) | 2003-05-20 | 2004-12-29 | Genentech, Inc. | Benzofuran inhibitors of factor VIIa |
| WO2004113278A2 (en) | 2003-05-20 | 2004-12-29 | Genentech, Inc. | Acylsulfamide inhibitors of factor viia |
| EP1680406A1 (en) * | 2003-10-29 | 2006-07-19 | Elan Pharmaceuticals, Inc. | N-substituted benzene sulfonamides |
| EP1533298A1 (en) | 2003-11-21 | 2005-05-25 | Newron Pharmaceuticals S.p.A. | 3-aminopyrrolidone derivatives |
| 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 |
| ATE517085T1 (de) * | 2004-11-23 | 2011-08-15 | Astrazeneca Ab | Zur behandlung von atemwegserkrankungen geeignete phenoxyessigsäurederivate |
| AU2006244206A1 (en) | 2005-05-10 | 2006-11-16 | Vertex Pharmaceuticals Incorporated | Bicyclic derivatives as modulators of ion channels |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
| AU2869092A (en) * | 1991-10-11 | 1993-05-03 | Smithkline Beecham Corporation | Heterocyclic 3-phenylpyrrolidin-2-ones, their preparation and use for the manufacture of a medicament for inhibiting tumor necrosis factor production |
| JPH05201971A (ja) * | 1992-01-28 | 1993-08-10 | Hokuriku Seiyaku Co Ltd | 環状アミン含有ベンゼンスルホンアミド誘導体 |
| US5665754A (en) * | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| WO1995008533A1 (en) * | 1993-09-21 | 1995-03-30 | Yamanouchi Pharmaceutical Co., Ltd. | N-(3-pyrrolidinyl)benzamide derivative |
| FR2714378B1 (fr) * | 1993-12-24 | 1996-03-15 | Sanofi Sa | Dérivés de l'indol-2-one substitués en 3 par un groupe azoté, leur préparation, les compositions pharmaceutiques en contenant. |
-
1995
- 1995-06-07 US US08/481,024 patent/US5612353A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 CN CN96194489A patent/CN1190395A/zh active Pending
- 1996-06-07 SK SK1606-97A patent/SK160697A3/sk unknown
- 1996-06-07 AT AT96919298T patent/ATE520655T1/de not_active IP Right Cessation
- 1996-06-07 AU AU61669/96A patent/AU714319B2/en not_active Ceased
- 1996-06-07 SI SI9620093A patent/SI9620093A/sl unknown
- 1996-06-07 EP EP96919298A patent/EP0853618B1/en not_active Expired - Lifetime
- 1996-06-07 AP APAP/P/1997/001144A patent/AP799A/en active
- 1996-06-07 WO PCT/US1996/009816 patent/WO1996040679A1/en not_active Ceased
- 1996-06-07 BR BR9608405A patent/BR9608405A/pt not_active Application Discontinuation
- 1996-06-07 PL PL96323780A patent/PL323780A1/xx unknown
- 1996-06-07 HU HU9801882A patent/HUP9801882A3/hu unknown
- 1996-06-07 EA EA199800043A patent/EA000700B1/ru not_active IP Right Cessation
- 1996-06-07 CA CA002223403A patent/CA2223403C/en not_active Expired - Fee Related
- 1996-06-07 KR KR1019970708866A patent/KR100291711B1/ko not_active Expired - Fee Related
- 1996-06-07 CZ CZ973853A patent/CZ385397A3/cs unknown
- 1996-06-07 JP JP50202997A patent/JP4312829B2/ja not_active Expired - Fee Related
-
1997
- 1997-12-03 OA OA70149A patent/OA10752A/en unknown
- 1997-12-08 NO NO19975762A patent/NO310457B1/no unknown
- 1997-12-08 MX MX9709977A patent/MX9709977A/es not_active IP Right Cessation
-
1998
- 1998-01-06 BG BG102162A patent/BG63628B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE520655T1 (de) | 2011-09-15 |
| NO975762L (no) | 1998-02-06 |
| CN1190395A (zh) | 1998-08-12 |
| EP0853618B1 (en) | 2011-08-17 |
| HUP9801882A2 (hu) | 1998-12-28 |
| EA000700B1 (ru) | 2000-02-28 |
| OA10752A (en) | 2001-07-04 |
| KR100291711B1 (ko) | 2001-09-17 |
| AU6166996A (en) | 1996-12-30 |
| EP0853618A4 (en) | 2000-03-15 |
| HUP9801882A3 (en) | 1999-01-28 |
| WO1996040679A1 (en) | 1996-12-19 |
| US5612353A (en) | 1997-03-18 |
| BR9608405A (pt) | 1999-08-24 |
| BG63628B1 (bg) | 2002-07-31 |
| EP0853618A1 (en) | 1998-07-22 |
| AP799A (en) | 2000-01-19 |
| PL323780A1 (en) | 1998-04-27 |
| CA2223403C (en) | 2002-04-23 |
| BG102162A (en) | 1998-09-30 |
| CA2223403A1 (en) | 1996-12-19 |
| NO975762D0 (no) | 1997-12-08 |
| AP9701144A0 (en) | 1998-01-31 |
| MX9709977A (es) | 1998-07-31 |
| JP4312829B2 (ja) | 2009-08-12 |
| EA199800043A1 (ru) | 1998-08-27 |
| CZ385397A3 (cs) | 1999-05-12 |
| AU714319B2 (en) | 2000-01-06 |
| KR19990022386A (ko) | 1999-03-25 |
| SK160697A3 (en) | 1998-11-04 |
| JPH11507368A (ja) | 1999-06-29 |
| NO310457B1 (no) | 2001-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SI9620093A (sl) | Substituirane (sulfinska kislina, sulfonska kislina, sulfonilamino ali sulfinilamino) N-/(aminoiminometil)fenilalkil/-azaheterociklilamidne spojine | |
| AU727810B2 (en) | Substituted sulfonic acid N-((aminoiminomethyl) phenylalkyl)-azaheterocyclamide compounds | |
| FI111007B (fi) | Menetelmä terapeuttisesti aktiivisten 1-amidinofenyyli-pyrrolidonien, -piperidinonien ja -atsetinonien valmistamiseksi | |
| US6218389B1 (en) | Acyclic metalloprotease inhibitors | |
| KR100348338B1 (ko) | 치환된n-[(아미노이미노메틸또는아미노메틸)페닐]프로필아미드및이를포함하는약제학적조성물 | |
| EP1856096B1 (en) | Phenylglycinamide derivatives useful as anticoagulants | |
| UA59433C2 (uk) | ЗАМІЩЕНІ ОКСОАЗАГЕТЕРОЦИКЛІЧНІ ІНГІБІТОРИ ФАКТОРА Хa ТА ПРОМІЖНІ СПОЛУКИ ДЛЯ ЇХ ОТРИМАННЯ | |
| SK8292003A3 (en) | Carboxylic acid amide derivatives and their use in the treatment of thromboembolic diseases and tumours | |
| BRPI0708782A2 (pt) | derivado de triazol ou um sal deste | |
| TW200922556A (en) | Novel cathepsin C inhibitors and their use | |
| US6034093A (en) | Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds | |
| DE69709933T2 (de) | Aromatische amidinderivate als selektive thrombininhibitoren | |
| BRPI0620254A2 (pt) | inibidores do fator viia macrocìclicos úteis como anticoagulantes, bem como composição farmaceutica compreendendo os mesmos e uso | |
| KR20010102968A (ko) | 시클릭 화합물 | |
| US5958918A (en) | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N- (aminominomethyl)phenylalkyl!-azaheterocyclylamide compounds | |
| EP1317428B1 (en) | Pyrrolidine-2-carboxylic acid hydrazide derivatives for use as metalloprotease inhibitors |