SK71299A3 - Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds - Google Patents

Info

Publication number

SK71299A3

SK71299A3 SK712-99A SK71299A SK71299A3 SK 71299 A3 SK71299 A3 SK 71299A3 SK 71299 A SK71299 A SK 71299A SK 71299 A3 SK71299 A3 SK 71299A3

Authority

SK

Slovakia

Prior art keywords

ylmethyl

sulfonic acid

oxo

amide

pyrrolidin

Prior art date

1996-12-13

Links

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• Global Dossier
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• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title claims description 8
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 477
• 108010074860 Factor Xa Proteins 0.000 claims abstract description 32
• 230000000694 effects Effects 0.000 claims abstract description 25
• 238000011282 treatment Methods 0.000 claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• -1 1-amino-isoquinol-7-ylmethyl Chemical group 0.000 claims description 187
• 229910052739 hydrogen Inorganic materials 0.000 claims description 79
• 229910052757 nitrogen Inorganic materials 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 62
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 51
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 48
• 239000002253 acid Substances 0.000 claims description 45
• 150000001408 amides Chemical class 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 42
• 150000003839 salts Chemical class 0.000 claims description 42
• 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 41
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
• 125000001072 heteroaryl group Chemical group 0.000 claims description 37
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 24
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• 230000015572 biosynthetic process Effects 0.000 claims description 21
• 230000002792 vascular Effects 0.000 claims description 21
• 239000003146 anticoagulant agent Substances 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 125000003107 substituted aryl group Chemical group 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 208000007536 Thrombosis Diseases 0.000 claims description 13
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• 238000002560 therapeutic procedure Methods 0.000 claims description 12
• 206010053567 Coagulopathies Diseases 0.000 claims description 10
• 125000002252 acyl group Chemical group 0.000 claims description 10
• 125000003277 amino group Chemical group 0.000 claims description 10
• 125000004434 sulfur atom Chemical group 0.000 claims description 10
• BSXLLFUSNQCWJP-UHFFFAOYSA-N thiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-N 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000005493 quinolyl group Chemical group 0.000 claims description 9
• 230000001154 acute effect Effects 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 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 7
• 210000001367 artery Anatomy 0.000 claims description 7
• 208000035475 disorder Diseases 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 210000003462 vein Anatomy 0.000 claims description 7
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 206010000891 acute myocardial infarction Diseases 0.000 claims description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000001624 naphthyl group Chemical group 0.000 claims description 6
• 230000001575 pathological effect Effects 0.000 claims description 6
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
• 238000001356 surgical procedure Methods 0.000 claims description 6
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
• 238000007887 coronary angioplasty Methods 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 5
• 230000002093 peripheral effect Effects 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
• 208000005189 Embolism Diseases 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 208000001435 Thromboembolism Diseases 0.000 claims description 4
• 208000007814 Unstable Angina Diseases 0.000 claims description 4
• 206010053648 Vascular occlusion Diseases 0.000 claims description 4
• 208000036142 Viral infection Diseases 0.000 claims description 4
• 230000002159 abnormal effect Effects 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
• 210000003127 knee Anatomy 0.000 claims description 4
• 230000007774 longterm Effects 0.000 claims description 4
• 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 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
• 230000002537 thrombolytic effect Effects 0.000 claims description 4
• 208000021331 vascular occlusion disease Diseases 0.000 claims description 4
• 230000009385 viral infection Effects 0.000 claims description 4
• 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 3
• ZGIAFQOCODFJFG-FERBBOLQSA-N 6-chloro-n-[(3s)-1-[(1,6-diaminoisoquinolin-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=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC4=C(N)N=CC=C4C=C3N)=CC2=C1 ZGIAFQOCODFJFG-FERBBOLQSA-N 0.000 claims description 3
• 230000003187 abdominal effect Effects 0.000 claims description 3
• 125000005466 alkylenyl group Chemical group 0.000 claims description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 210000003141 lower extremity Anatomy 0.000 claims description 3
• 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 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
• 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 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
• 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 3
• GIHMCGIGPTWOSC-VIFPVBQESA-N (3s)-3-amino-1-(furo[3,2-b]pyridin-2-ylmethyl)pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1CC1=CC2=NC=CC=C2O1 GIHMCGIGPTWOSC-VIFPVBQESA-N 0.000 claims description 2
• GRZHOJRWTBYXAL-UHFFFAOYSA-N 7-methoxy-n-[2-oxo-1-[(1-oxo-2h-isoquinolin-7-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=CN=C(O)C2=CC(CN3CCC(C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 GRZHOJRWTBYXAL-UHFFFAOYSA-N 0.000 claims description 2
• PJYDEUGKSDYXSC-FVGYRXGTSA-N N[C@@H](CCN1CC2=CC(C(Cl)=NC=C3)=C3N2)C1=O.ClC1=CC(SC=C2)=C2C=C1 Chemical compound N[C@@H](CCN1CC2=CC(C(Cl)=NC=C3)=C3N2)C1=O.ClC1=CC(SC=C2)=C2C=C1 PJYDEUGKSDYXSC-FVGYRXGTSA-N 0.000 claims description 2
• 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• XQYHQVFBDDWDCG-GNAFDRTKSA-N n-[(3r)-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-GNAFDRTKSA-N 0.000 claims description 2
• 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 2
• QFZAMTBGXXFFQX-LMOVPXPDSA-N n-[(3s)-1-[(2-aminoquinolin-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)CC=3C=CC4=CC=C(N=C4C=3)N)=CC2=C1 QFZAMTBGXXFFQX-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
• GNLWVDZSQAGWPX-NTISSMGPSA-N n-[(3s)-2-oxo-1-(thieno[3,2-c]pyridin-2-ylmethyl)pyrrolidin-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]3C(N(CC3)CC=3SC4=CC=NC=C4C=3)=O)=CC2=C1 GNLWVDZSQAGWPX-NTISSMGPSA-N 0.000 claims description 2
• 239000012453 solvate Substances 0.000 claims description 2
• 206010022562 Intermittent claudication Diseases 0.000 claims 2
• 208000021156 intermittent vascular claudication Diseases 0.000 claims 2
• 238000012423 maintenance Methods 0.000 claims 2
• 238000007891 venous angioplasty Methods 0.000 claims 2
• BYSHGJJHECFJFF-YDALLXLXSA-N (3S)-3-amino-1-[(1-aminoisoquinolin-6-yl)methyl]pyrrolidin-2-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](N)CCN1CC1=CC=C(C(N)=NC=C2)C2=C1 BYSHGJJHECFJFF-YDALLXLXSA-N 0.000 claims 1
• RLROINLSAMVACI-MERQFXBCSA-N (3S)-3-amino-1-[(2-aminoquinolin-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=CC=C(C=CC(N)=N2)C2=C1 RLROINLSAMVACI-MERQFXBCSA-N 0.000 claims 1
• JAEKEOJFYOBMBH-DEOSSOPVSA-N 7-methoxy-n-methyl-n-[(3s)-2-oxo-1-[(2-oxo-1h-quinolin-7-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=CC(=O)NC2=CC(CN3CC[C@@H](C3=O)N(C)S(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 JAEKEOJFYOBMBH-DEOSSOPVSA-N 0.000 claims 1
• 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 1
• 206010010904 Convulsion Diseases 0.000 claims 1
• KYQHQDPOXYFBJH-FYZYNONXSA-N FC(C(=O)O)(F)F.NN1CC2=CC(=CC=C2C=C1)CN1C([C@H](CC1)NS(=O)(=O)C1=CC2=C(S1)C=C(C=C2)Cl)=O Chemical compound FC(C(=O)O)(F)F.NN1CC2=CC(=CC=C2C=C1)CN1C([C@H](CC1)NS(=O)(=O)C1=CC2=C(S1)C=C(C=C2)Cl)=O KYQHQDPOXYFBJH-FYZYNONXSA-N 0.000 claims 1
• 208000006011 Stroke Diseases 0.000 claims 1
• 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
• 238000002399 angioplasty Methods 0.000 claims 1
• 125000005605 benzo group Chemical group 0.000 claims 1
• 210000004351 coronary vessel Anatomy 0.000 claims 1
• 150000003949 imides Chemical class 0.000 claims 1
• 208000015181 infectious disease Diseases 0.000 claims 1
• 230000000302 ischemic effect Effects 0.000 claims 1
• 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 1
• 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 1
• NNRYOTUHJOSHQZ-DEOSSOPVSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-n-methylnaphthalene-2-sulfonamide Chemical compound C1=CN=C(N)C2=CC(CN3CC[C@@H](C3=O)N(C)S(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 NNRYOTUHJOSHQZ-DEOSSOPVSA-N 0.000 claims 1
• ORCXLRODECQKBO-JIDHJSLPSA-N n-[(3s)-1-[(2-aminoquinolin-5-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-n-methylnaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC1=CC=C2C(CN3CC[C@@H](C3=O)N(C)S(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=CC2=N1 ORCXLRODECQKBO-JIDHJSLPSA-N 0.000 claims 1
• WREGTDSWOJUCLO-IBGZPJMESA-N n-[(3s)-1-[(4-aminothieno[2,3-d]pyrimidin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound N1=CN=C2SC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1N WREGTDSWOJUCLO-IBGZPJMESA-N 0.000 claims 1
• KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 claims 1
• 229910021653 sulphate ion Inorganic materials 0.000 claims 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 claims 1
• 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
• 230000001052 transient effect Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 104
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• 230000000144 pharmacologic effect Effects 0.000 abstract description 5
• 230000004962 physiological condition Effects 0.000 abstract description 3
• 230000001668 ameliorated effect Effects 0.000 abstract description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 513
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 423
• 239000000243 solution Substances 0.000 description 296
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 279
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 279
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 231
• 238000005481 NMR spectroscopy Methods 0.000 description 209
• 239000007787 solid Substances 0.000 description 183
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 164
• 239000012043 crude product Substances 0.000 description 114
• 238000004440 column chromatography Methods 0.000 description 92
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
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• 239000000047 product Substances 0.000 description 71
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
• 239000000460 chlorine Substances 0.000 description 61
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• 239000012044 organic layer Substances 0.000 description 57
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 53
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
• 238000004007 reversed phase HPLC Methods 0.000 description 42
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