CA2274686C - Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds - Google Patents

Info

Publication number

CA2274686C

CA2274686C CA002274686A CA2274686A CA2274686C CA 2274686 C CA2274686 C CA 2274686C CA 002274686 A CA002274686 A CA 002274686A CA 2274686 A CA2274686 A CA 2274686A CA 2274686 C CA2274686 C CA 2274686C

Authority

CA

Canada

Prior art keywords

sulfonic acid

oxopyrrolidin

ylmethyl

optionally substituted

chloro

Prior art date

1996-12-13

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

Expired - Fee Related

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• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title description 3
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 409
• 108010074860 Factor Xa Proteins 0.000 claims abstract description 32
• 230000000694 effects Effects 0.000 claims abstract description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
• -1 amide trifluoroacetate Chemical class 0.000 claims description 114
• 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 62
• 229910052757 nitrogen Inorganic materials 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 229910052760 oxygen Inorganic materials 0.000 claims description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
• 150000003839 salts Chemical class 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 42
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
• 125000001072 heteroaryl group Chemical group 0.000 claims description 32
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 31
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
• 239000001257 hydrogen Substances 0.000 claims description 25
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 24
• 239000003146 anticoagulant agent Substances 0.000 claims description 22
• 125000000623 heterocyclic group Chemical group 0.000 claims description 17
• 230000015572 biosynthetic process Effects 0.000 claims description 16
• 208000007536 Thrombosis Diseases 0.000 claims description 15
• 125000003107 substituted aryl group Chemical group 0.000 claims description 14
• 238000002560 therapeutic procedure Methods 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• 150000001408 amides Chemical class 0.000 claims description 12
• 230000002792 vascular Effects 0.000 claims description 12
• KTVOMLQUDMNZLK-UHFFFAOYSA-N 1-benzothiophene-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=C1 KTVOMLQUDMNZLK-UHFFFAOYSA-N 0.000 claims description 11
• 125000002252 acyl group Chemical group 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• ZYDGKFWFDVZKMG-UHFFFAOYSA-N 6-chloro-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2SC(S(=O)(=O)O)=CC2=C1 ZYDGKFWFDVZKMG-UHFFFAOYSA-N 0.000 claims description 9
• 206010053567 Coagulopathies Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
• 230000001154 acute effect Effects 0.000 claims description 8
• 210000001367 artery Anatomy 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 210000003462 vein Anatomy 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
• 206010000891 acute myocardial infarction Diseases 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 125000001624 naphthyl group Chemical group 0.000 claims description 6
• 230000001575 pathological effect Effects 0.000 claims description 6
• 230000002093 peripheral effect Effects 0.000 claims description 6
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 125000005605 benzo group Chemical group 0.000 claims description 5
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
• 238000012423 maintenance Methods 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 208000037803 restenosis Diseases 0.000 claims description 5
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
• 238000001356 surgical procedure Methods 0.000 claims description 5
• 230000002537 thrombolytic effect Effects 0.000 claims description 5
• 210000005166 vasculature Anatomy 0.000 claims description 5
• 206010002388 Angina unstable Diseases 0.000 claims description 4
• 206010022562 Intermittent claudication Diseases 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 208000032109 Transient ischaemic attack Diseases 0.000 claims description 4
• 208000007814 Unstable Angina Diseases 0.000 claims description 4
• 230000003187 abdominal effect Effects 0.000 claims description 4
• 230000002159 abnormal effect Effects 0.000 claims description 4
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
• 229940092714 benzenesulfonic acid Drugs 0.000 claims description 4
• 208000015294 blood coagulation disease Diseases 0.000 claims description 4
• 238000001631 haemodialysis Methods 0.000 claims description 4
• 230000000322 hemodialysis Effects 0.000 claims description 4
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
• 208000021156 intermittent vascular claudication Diseases 0.000 claims description 4
• 210000003127 knee Anatomy 0.000 claims description 4
• 230000007774 longterm Effects 0.000 claims description 4
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
• 230000036303 septic shock Effects 0.000 claims description 4
• 230000009885 systemic effect Effects 0.000 claims description 4
• 201000010875 transient cerebral ischemia Diseases 0.000 claims description 4
• GNSUPVVLHBGDAU-QHCPKHFHSA-N 7-methoxy-n-[(3s)-2-oxo-1-[(2-oxo-1h-quinolin-6-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound N1=C(O)C=CC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 GNSUPVVLHBGDAU-QHCPKHFHSA-N 0.000 claims description 3
• 208000005189 Embolism Diseases 0.000 claims description 3
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 208000001435 Thromboembolism Diseases 0.000 claims description 3
• 208000036142 Viral infection Diseases 0.000 claims description 3
• 125000005466 alkylenyl group Chemical group 0.000 claims description 3
• 210000005249 arterial vasculature Anatomy 0.000 claims description 3
• 238000007887 coronary angioplasty Methods 0.000 claims description 3
• 210000003141 lower extremity Anatomy 0.000 claims description 3
• VFHQLCGAUYJSRP-FERBBOLQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4C=CN=C(C4=C3)N)=CC2=C1 VFHQLCGAUYJSRP-FERBBOLQSA-N 0.000 claims description 3
• VCVKZPRYRNNAHF-FYZYNONXSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-3-ylthiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H]1CCN(C1=O)CC1=CC=C2C=CN=C(C2=C1)N)S(=O)(=O)C(S1)=CC=C1C1=CC=CN=C1 VCVKZPRYRNNAHF-FYZYNONXSA-N 0.000 claims description 3
• CDIMXWPYBBXLPZ-FYZYNONXSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-4-ylthiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H]1CCN(C1=O)CC1=CC=C2C=CN=C(C2=C1)N)S(=O)(=O)C(S1)=CC=C1C1=CC=NC=C1 CDIMXWPYBBXLPZ-FYZYNONXSA-N 0.000 claims description 3
• XQYHQVFBDDWDCG-BQAIUKQQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CN=C(N)C2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 XQYHQVFBDDWDCG-BQAIUKQQSA-N 0.000 claims description 3
• 238000010577 post-coronary angioplasty Methods 0.000 claims description 3
• 230000009385 viral infection Effects 0.000 claims description 3
• SBJNVOOUBMGMKV-FVGYRXGTSA-N (3S)-3-amino-1-(3H-benzimidazol-5-ylmethyl)pyrrolidin-2-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](N)CCN1CC1=CC=C(N=CN2)C2=C1 SBJNVOOUBMGMKV-FVGYRXGTSA-N 0.000 claims description 2
• VARXSWARIPTRNM-BDQAORGHSA-N 7-methoxy-n-[(3s)-2-oxo-1-[(7-oxo-6h-thieno[2,3-c]pyridin-3-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CNC(=O)C2=C1C(CN1CC[C@@H](C1=O)NS(=O)(=O)C=1C=CC3=CC=C(C=C3C=1)OC)=CS2 VARXSWARIPTRNM-BDQAORGHSA-N 0.000 claims description 2
• DRNPKIQESPNKGA-GXKRWWSZSA-N CN[C@@H](CCN1CC2=C(C=CC(N)=N3)C3=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=C(C=CC(N)=N3)C3=CC=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O DRNPKIQESPNKGA-GXKRWWSZSA-N 0.000 claims description 2
• ZCCRHCDYAANSFJ-ZOWNYOTGSA-N CN[C@@H](CCN1CC2=C(C=CC(N3)=O)C3=CC=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1 Chemical compound CN[C@@H](CCN1CC2=C(C=CC(N3)=O)C3=CC=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1 ZCCRHCDYAANSFJ-ZOWNYOTGSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims description 2
• CVQMJHHVBFGTFG-BQAIUKQQSA-N n-[(3s)-1-[(1,6-diaminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC=C2C=C(N)C(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1N CVQMJHHVBFGTFG-BQAIUKQQSA-N 0.000 claims description 2
• HZBSKFFTPFUHBU-BQAIUKQQSA-N n-[(3s)-1-[(1-amino-6-methoxyisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;hydrochloride Chemical compound Cl.N1=CC=C2C=C(OC)C(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1N HZBSKFFTPFUHBU-BQAIUKQQSA-N 0.000 claims description 2
• WNQJRFJOLDUOFH-FERBBOLQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4C=CN=C(C4=C3)N)=CC2=C1 WNQJRFJOLDUOFH-FERBBOLQSA-N 0.000 claims description 2
• QTMHKYIZBVUMKD-QHCPKHFHSA-N n-[(3s)-1-[(2-aminoquinolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound N1=C(N)C=CC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 QTMHKYIZBVUMKD-QHCPKHFHSA-N 0.000 claims description 2
• SEYWMQRAUGNBSI-LMOVPXPDSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC=3C=CC4=CC=C(N=C4C=3)N)=CC2=C1 SEYWMQRAUGNBSI-LMOVPXPDSA-N 0.000 claims description 2
• MMPKCFIXJKMLPC-FTBISJDPSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(N)=NC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 MMPKCFIXJKMLPC-FTBISJDPSA-N 0.000 claims description 2
• KHZHBQZHEIZBHY-FYZYNONXSA-N n-[(3s)-1-[(4-aminoquinolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4N=CC=C(C4=C3)N)=CC2=C1 KHZHBQZHEIZBHY-FYZYNONXSA-N 0.000 claims description 2
• XQYHQVFBDDWDCG-UHFFFAOYSA-N n-[1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CN=C(N)C2=CC(CN3CCC(C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 XQYHQVFBDDWDCG-UHFFFAOYSA-N 0.000 claims description 2
• JKVVUQHCNMNTQL-UHFFFAOYSA-N n-[1-[(4-aminothieno[3,2-c]pyridin-3-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=NC(N)=C2C(CN3CCC(C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CSC2=C1 JKVVUQHCNMNTQL-UHFFFAOYSA-N 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 claims description 2
• 239000012453 solvate Substances 0.000 claims description 2
• UVLKAUNUFWQFID-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=N1 UVLKAUNUFWQFID-UHFFFAOYSA-N 0.000 claims description 2
• 229910052721 tungsten Inorganic materials 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 8
• DCVXLCIPWIKDJU-BOXHHOBZSA-N 7-methoxy-n-[(3s)-2-oxo-1-(1h-pyrrolo[3,2-b]pyridin-2-ylmethyl)pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=N1 DCVXLCIPWIKDJU-BOXHHOBZSA-N 0.000 claims 2
• 238000007891 venous angioplasty Methods 0.000 claims 2
• RROZPQBCANKSJH-GXKRWWSZSA-N (3S)-1-[(1-aminoisoquinolin-7-yl)methyl]-3-(methylamino)pyrrolidin-2-one 7-methoxynaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound CN[C@@H](CCN1CC2=CC=C(C=CN=C3N)C3=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O RROZPQBCANKSJH-GXKRWWSZSA-N 0.000 claims 1
• UVZYXTNMWPQUNE-LTCKWSDVSA-N (3S)-1-[(4-aminoquinazolin-6-yl)methyl]-3-(methylamino)pyrrolidin-2-one 7-methoxynaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound CN[C@@H](CCN1CC(C=C23)=CC=C2N=CN=C3N)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O UVZYXTNMWPQUNE-LTCKWSDVSA-N 0.000 claims 1
• JXVRJRAGBVISSM-PPHPATTJSA-N (3S)-3-amino-1-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pyrrolidin-2-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](N)CCN1CC1=CC2=CC=NC=C2N1 JXVRJRAGBVISSM-PPHPATTJSA-N 0.000 claims 1
• BNTNYSKQEQVEPH-MERQFXBCSA-N (3S)-3-amino-1-[(1,6-diaminoisoquinolin-7-yl)methyl]pyrrolidin-2-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](N)CCN1CC1=CC2=C(N)N=CC=C2C=C1N BNTNYSKQEQVEPH-MERQFXBCSA-N 0.000 claims 1
• IJZYUSAXPDDIKX-HNNXBMFYSA-N 6-chloro-n-[(3s)-1-(furo[3,2-b]pyridin-2-ylmethyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound C1=CC=C2OC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=N1 IJZYUSAXPDDIKX-HNNXBMFYSA-N 0.000 claims 1
• ROMBXSYEYVFYBT-INIZCTEOSA-N 6-chloro-n-[(3s)-1-[(4-chloro-1h-pyrrolo[3,2-c]pyridin-2-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound N1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=C1Cl ROMBXSYEYVFYBT-INIZCTEOSA-N 0.000 claims 1
• NILRJQHBKCPZCU-FYZYNONXSA-N 6-chloro-n-[(3s)-2-oxo-1-(1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CNCC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC=C21 NILRJQHBKCPZCU-FYZYNONXSA-N 0.000 claims 1
• WFPXVTGXHWCEQC-JIDHJSLPSA-N 7-methoxy-n-[(3s)-1-[(6-methoxyisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC=C2C=C(OC)C(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1 WFPXVTGXHWCEQC-JIDHJSLPSA-N 0.000 claims 1
• RROZPQBCANKSJH-UHFFFAOYSA-N CNC(CCN1CC2=CC=C(C=CN=C3N)C3=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O Chemical compound CNC(CCN1CC2=CC=C(C=CN=C3N)C3=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O RROZPQBCANKSJH-UHFFFAOYSA-N 0.000 claims 1
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• ZWFHYRSGEGPXMO-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[(1-chloro-6-methoxyisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound COC1=CC2=CC=NC(Cl)=C2C=C1CN1CC[C@H](NC(=O)OC(C)(C)C)C1=O ZWFHYRSGEGPXMO-HNNXBMFYSA-N 0.000 description 1
• HKSOXCDXUDXKCF-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[(2-chloroquinolin-5-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=CC2=NC(Cl)=CC=C12 HKSOXCDXUDXKCF-HNNXBMFYSA-N 0.000 description 1
• RJPFCLUPDFYMAB-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[(2-chloroquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=C(C=CC(Cl)=N2)C2=C1 RJPFCLUPDFYMAB-AWEZNQCLSA-N 0.000 description 1
• FOZOGMITMOFFLE-NSHDSACASA-N tert-butyl n-[(3s)-1-[(4-chlorothieno[2,3-d]pyrimidin-6-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical group O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC2=C(Cl)N=CN=C2S1 FOZOGMITMOFFLE-NSHDSACASA-N 0.000 description 1
• LXNQETOYUOOORR-JTQLQIEISA-N tert-butyl n-[(3s)-1-[(4-chlorothieno[3,2-d]pyrimidin-7-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical group O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CSC2=C(Cl)N=CN=C12 LXNQETOYUOOORR-JTQLQIEISA-N 0.000 description 1
• JEQCOMGANLGZGA-SFHVURJKSA-N tert-butyl n-[(3s)-1-[[1-(benzenesulfonyl)-4-chloropyrrolo[3,2-c]pyridin-2-yl]methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC2=C(Cl)N=CC=C2N1S(=O)(=O)C1=CC=CC=C1 JEQCOMGANLGZGA-SFHVURJKSA-N 0.000 description 1
• WKHGDPZRLXDVMJ-UHFFFAOYSA-N tert-butyl n-pyridin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN=C1 WKHGDPZRLXDVMJ-UHFFFAOYSA-N 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
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
• KHXSHOAPGUCQLC-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=CC2=N1 KHXSHOAPGUCQLC-UHFFFAOYSA-N 0.000 description 1
• MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 1
• GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
• 230000002885 thrombogenetic effect Effects 0.000 description 1
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 210000003437 trachea Anatomy 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 229960001322 trypsin Drugs 0.000 description 1
• 229960005356 urokinase Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 238000005303 weighing 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