ES2289297T3 - Acido 3-mercaptopentanoico 2,5-disustituido. - Google Patents
Acido 3-mercaptopentanoico 2,5-disustituido. Download PDFInfo
- Publication number
- ES2289297T3 ES2289297T3 ES03730987T ES03730987T ES2289297T3 ES 2289297 T3 ES2289297 T3 ES 2289297T3 ES 03730987 T ES03730987 T ES 03730987T ES 03730987 T ES03730987 T ES 03730987T ES 2289297 T3 ES2289297 T3 ES 2289297T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- optionally substituted
- hydroxy
- halogen
- alkyl
- Prior art date
- 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 - Lifetime
Links
- PTPQZNNAUUSACC-UHFFFAOYSA-N 3-sulfanylpentanoic acid Chemical compound CCC(S)CC(O)=O PTPQZNNAUUSACC-UHFFFAOYSA-N 0.000 title description 2
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 90
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims abstract description 12
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 61
- 150000002367 halogens Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 108090000201 Carboxypeptidase B2 Proteins 0.000 claims description 24
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 24
- 102000003847 Carboxypeptidase B2 Human genes 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 230000001012 protector Effects 0.000 claims 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 57
- 239000002253 acid Substances 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 102000013566 Plasminogen Human genes 0.000 description 8
- 108010051456 Plasminogen Proteins 0.000 description 8
- 230000020764 fibrinolysis Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000010561 standard procedure Methods 0.000 description 7
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- 229940012957 plasmin Drugs 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000003176 fibrotic effect Effects 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 201000005665 thrombophilia Diseases 0.000 description 5
- PFIYKHNOMGYTGR-UHFFFAOYSA-N 3-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC(I)=C1 PFIYKHNOMGYTGR-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- JCFUBJSIMQRJLI-UHFFFAOYSA-N 3-(3-phenylphenyl)propanal Chemical compound O=CCCC1=CC=CC(C=2C=CC=CC=2)=C1 JCFUBJSIMQRJLI-UHFFFAOYSA-N 0.000 description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 101800004538 Bradykinin Proteins 0.000 description 3
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 102100035792 Kininogen-1 Human genes 0.000 description 3
- 108010085169 Lysine carboxypeptidase Proteins 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 101800004937 Protein C Proteins 0.000 description 3
- 102000017975 Protein C Human genes 0.000 description 3
- 101800001700 Saposin-D Proteins 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 235000018977 lysine Nutrition 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229960000856 protein c Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- SCSLUABEVMLYEA-UHFFFAOYSA-N tert-butyl pentanoate Chemical compound CCCCC(=O)OC(C)(C)C SCSLUABEVMLYEA-UHFFFAOYSA-N 0.000 description 3
- AVZDGFRDSOPFCR-UHFFFAOYSA-N tert-butyl-(3-iodophenoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(I)=C1 AVZDGFRDSOPFCR-UHFFFAOYSA-N 0.000 description 3
- YWTAVACCUJLZHY-UHFFFAOYSA-N 1-iodo-2-[(4-methoxyphenyl)methoxy]benzene Chemical compound C1=CC(OC)=CC=C1COC1=CC=CC=C1I YWTAVACCUJLZHY-UHFFFAOYSA-N 0.000 description 2
- BLAUWCSRSAQCDW-UHFFFAOYSA-N 1-iodo-3-[(4-methoxyphenyl)methoxymethyl]benzene Chemical compound C1=CC(OC)=CC=C1COCC1=CC=CC(I)=C1 BLAUWCSRSAQCDW-UHFFFAOYSA-N 0.000 description 2
- BGZLCAVXCGKSOA-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3-phenylphenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C=2C=CC=CC=2)=C1 BGZLCAVXCGKSOA-UHFFFAOYSA-N 0.000 description 2
- GHKHLSYKUQXGQL-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(4-methoxyphenyl)-3-sulfanylpentanoic acid Chemical compound C1=CC(OC)=CC=C1CCC(S)C(C(O)=O)CC1=CC=C(N)N=C1 GHKHLSYKUQXGQL-UHFFFAOYSA-N 0.000 description 2
- SENUJLQYGRLTRW-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[methyl(2-phenylethyl)carbamoyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C=1C=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=CC=1C(=O)N(C)CCC1=CC=CC=C1 SENUJLQYGRLTRW-UHFFFAOYSA-N 0.000 description 2
- QZQOEJYMWHYSTC-UHFFFAOYSA-N 3-iodo-n-methyl-n-(2-phenylethyl)benzenesulfonamide Chemical compound C=1C=CC(I)=CC=1S(=O)(=O)N(C)CCC1=CC=CC=C1 QZQOEJYMWHYSTC-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 206010003178 Arterial thrombosis Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 102100035023 Carboxypeptidase B2 Human genes 0.000 description 2
- 102000005367 Carboxypeptidases Human genes 0.000 description 2
- 108010006303 Carboxypeptidases Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 108010023197 Streptokinase Proteins 0.000 description 2
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 229940122388 Thrombin inhibitor Drugs 0.000 description 2
- 208000001435 Thromboembolism Diseases 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- ULXIGOHDMHEIJT-UHFFFAOYSA-N n-(cyanomethyl)-3-iodo-n-methylbenzenesulfonamide Chemical compound N#CCN(C)S(=O)(=O)C1=CC=CC(I)=C1 ULXIGOHDMHEIJT-UHFFFAOYSA-N 0.000 description 2
- UAVDPEDXNZJKFL-UHFFFAOYSA-N n-(furan-2-ylmethyl)-3-iodo-n-methylbenzenesulfonamide Chemical compound C=1C=CC(I)=CC=1S(=O)(=O)N(C)CC1=CC=CO1 UAVDPEDXNZJKFL-UHFFFAOYSA-N 0.000 description 2
- XAWHUDPNFDAEHP-INIZCTEOSA-N n-[[(2s)-1-(3-iodophenyl)sulfonylpyrrolidin-2-yl]methyl]aniline Chemical compound IC1=CC=CC(S(=O)(=O)N2[C@@H](CCC2)CNC=2C=CC=CC=2)=C1 XAWHUDPNFDAEHP-INIZCTEOSA-N 0.000 description 2
- SASNBVQSOZSTPD-UHFFFAOYSA-N n-methylphenethylamine Chemical compound CNCCC1=CC=CC=C1 SASNBVQSOZSTPD-UHFFFAOYSA-N 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 239000003868 thrombin inhibitor Substances 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- OCAJMURFVZWFPX-UHFFFAOYSA-N (4-iodophenyl)-phenylmethanone Chemical compound C1=CC(I)=CC=C1C(=O)C1=CC=CC=C1 OCAJMURFVZWFPX-UHFFFAOYSA-N 0.000 description 1
- VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- KAQUBIATNWQNRE-UHFFFAOYSA-N 1-iodo-3-phenylbenzene Chemical group IC1=CC=CC(C=2C=CC=CC=2)=C1 KAQUBIATNWQNRE-UHFFFAOYSA-N 0.000 description 1
- INQSIVIAFIXVBD-UHFFFAOYSA-N 2-(3-azabicyclo[3.2.1]octan-8-ylmethyl)-5-phenyl-3-sulfanylpentanoic acid Chemical compound C1NCC2CCC1C2CC(C(=O)O)C(S)CCC1=CC=CC=C1 INQSIVIAFIXVBD-UHFFFAOYSA-N 0.000 description 1
- YOMHQFWXGBVZGF-UHFFFAOYSA-N 2-[(2-amino-1,3-thiazol-5-yl)methyl]-5-phenyl-3-sulfanylpentanoic acid Chemical compound S1C(N)=NC=C1CC(C(O)=O)C(S)CCC1=CC=CC=C1 YOMHQFWXGBVZGF-UHFFFAOYSA-N 0.000 description 1
- OWYXPHVFDZWODI-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-sulfanyl-5-(3,4,5-trimethoxyphenyl)pentanoic acid Chemical compound COC1=C(OC)C(OC)=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 OWYXPHVFDZWODI-UHFFFAOYSA-N 0.000 description 1
- VJEAHRBYELMNAU-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-sulfanyl-5-(thiolan-2-yl)pentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1SCCC1 VJEAHRBYELMNAU-UHFFFAOYSA-N 0.000 description 1
- OICDOYMXQJAIOR-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-sulfanyl-5-[4-(trifluoromethoxy)phenyl]pentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(OC(F)(F)F)C=C1 OICDOYMXQJAIOR-UHFFFAOYSA-N 0.000 description 1
- NVWXSSYGIAHNNN-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(1,3-benzodioxol-5-yl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(OCO2)C2=C1 NVWXSSYGIAHNNN-UHFFFAOYSA-N 0.000 description 1
- OZBQUEKMPLDCGU-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(1,3-dimethyl-2,4-dioxopyrimidin-5-yl)-3-sulfanylpentanoic acid Chemical compound O=C1N(C)C(=O)N(C)C=C1CCC(S)C(C(O)=O)CC1=CC=C(N)N=C1 OZBQUEKMPLDCGU-UHFFFAOYSA-N 0.000 description 1
- YWUWVCSFQAMZPC-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(2-hydroxyphenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC=C1O YWUWVCSFQAMZPC-UHFFFAOYSA-N 0.000 description 1
- TYMUJZDBOYNDOT-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3,5-dimethylphenyl)-3-sulfanylpentanoic acid Chemical compound CC1=CC(C)=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 TYMUJZDBOYNDOT-UHFFFAOYSA-N 0.000 description 1
- BVMYLKDQYMOYCM-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3-carbamoylphenyl)-3-sulfanylpentanoic acid Chemical compound NC(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 BVMYLKDQYMOYCM-UHFFFAOYSA-N 0.000 description 1
- CHKJKSYGEVLEQH-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3-chlorophenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(Cl)=C1 CHKJKSYGEVLEQH-UHFFFAOYSA-N 0.000 description 1
- RKLOIHSOHLMSNZ-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3-cyanophenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C#N)=C1 RKLOIHSOHLMSNZ-UHFFFAOYSA-N 0.000 description 1
- HYQSEQOTXIKWJP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(3-ethoxycarbonylphenyl)-3-sulfanylpentanoic acid Chemical compound CCOC(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 HYQSEQOTXIKWJP-UHFFFAOYSA-N 0.000 description 1
- RIIQDYXFTQDTPQ-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(4-benzylphenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC(C=C1)=CC=C1CC1=CC=CC=C1 RIIQDYXFTQDTPQ-UHFFFAOYSA-N 0.000 description 1
- AAZNRVZWKGMNRD-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(4-hydroxyphenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(O)C=C1 AAZNRVZWKGMNRD-UHFFFAOYSA-N 0.000 description 1
- IMEDFDYNHKHFKD-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(4-propylphenyl)-3-sulfanylpentanoic acid Chemical compound C1=CC(CCC)=CC=C1CCC(S)C(C(O)=O)CC1=CC=C(N)N=C1 IMEDFDYNHKHFKD-UHFFFAOYSA-N 0.000 description 1
- VOYNFTZMOOQJJQ-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-(4-sulfamoylphenyl)-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(S(N)(=O)=O)C=C1 VOYNFTZMOOQJJQ-UHFFFAOYSA-N 0.000 description 1
- DMWMENJDPREQBY-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[2-(2,4-dichlorophenoxy)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl DMWMENJDPREQBY-UHFFFAOYSA-N 0.000 description 1
- NXWSMEUDLDSVLN-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[2-fluoro-4-(trifluoromethyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(C(F)(F)F)C=C1F NXWSMEUDLDSVLN-UHFFFAOYSA-N 0.000 description 1
- XZCRKCYMXOMRLS-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(2-fluoroethylcarbamoyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)NCCF)=C1 XZCRKCYMXOMRLS-UHFFFAOYSA-N 0.000 description 1
- GDKPBFBUUBKLJF-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(2-pyridin-2-ylethoxycarbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)OCCC=2N=CC=CC=2)=C1 GDKPBFBUUBKLJF-UHFFFAOYSA-N 0.000 description 1
- LQFDKFVQMLYWMG-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(3-hydroxypyrrolidine-1-carbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N2CC(O)CC2)=C1 LQFDKFVQMLYWMG-UHFFFAOYSA-N 0.000 description 1
- PPANLYUWKBMCIM-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(3-oxopiperazine-1-carbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N2CC(=O)NCC2)=C1 PPANLYUWKBMCIM-UHFFFAOYSA-N 0.000 description 1
- HKVYWQRGCKEKKY-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(4-ethoxycarbonylpiperidine-1-carbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 HKVYWQRGCKEKKY-UHFFFAOYSA-N 0.000 description 1
- DLTDXTQIPIDJDN-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinoline-2-carbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(=O)C(C=1)=CC=CC=1CCC(S)C(C(O)=O)CC1=CC=C(N)N=C1 DLTDXTQIPIDJDN-UHFFFAOYSA-N 0.000 description 1
- NWFCKNQHGPVJAP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(dibenzylcarbamoyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 NWFCKNQHGPVJAP-UHFFFAOYSA-N 0.000 description 1
- PZGVBXFAZNVUKY-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(dimethylcarbamoyl)phenyl]-3-sulfanylpentanoic acid Chemical compound CN(C)C(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 PZGVBXFAZNVUKY-UHFFFAOYSA-N 0.000 description 1
- PCOYNXQWWOJLDT-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(ethenylcarbamoyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)NC=C)=C1 PCOYNXQWWOJLDT-UHFFFAOYSA-N 0.000 description 1
- XWAAAGUOAKZZQT-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(hydroxymethyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(CO)=C1 XWAAAGUOAKZZQT-UHFFFAOYSA-N 0.000 description 1
- DFKFCIYYHJXRSX-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(oxolan-3-ylmethoxy)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(OCC2COCC2)=C1 DFKFCIYYHJXRSX-UHFFFAOYSA-N 0.000 description 1
- POZUTGZIDBBMDP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(oxolan-3-yloxy)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(OC2COCC2)=C1 POZUTGZIDBBMDP-UHFFFAOYSA-N 0.000 description 1
- NVOOULUSLCGFBF-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-(pyrrolidine-1-carbonyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N2CCCC2)=C1 NVOOULUSLCGFBF-UHFFFAOYSA-N 0.000 description 1
- MUNYGOZCIMDVNS-XPWZEYHZSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[(2s)-2-(anilinomethyl)pyrrolidin-1-yl]sulfonylphenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(S(=O)(=O)N2[C@@H](CCC2)CNC=2C=CC=CC=2)=C1 MUNYGOZCIMDVNS-XPWZEYHZSA-N 0.000 description 1
- MJPPXTALPKZRBU-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[2-(2,6-dichlorophenyl)ethoxycarbonyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)OCCC=2C(=CC=CC=2Cl)Cl)=C1 MJPPXTALPKZRBU-UHFFFAOYSA-N 0.000 description 1
- WVPURSYLFOMONL-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[2-hydroxyethyl(methyl)carbamoyl]phenyl]-3-sulfanylpentanoic acid Chemical compound OCCN(C)C(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 WVPURSYLFOMONL-UHFFFAOYSA-N 0.000 description 1
- PJLBXZIVAZQWCA-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[4-(4-chlorophenyl)piperazine-1-carbonyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N2CCN(CC2)C=2C=CC(Cl)=CC=2)=C1 PJLBXZIVAZQWCA-UHFFFAOYSA-N 0.000 description 1
- BCDAOQHGDOADCE-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[4-(hydroxymethyl)piperidine-1-carbonyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(=O)N2CCC(CO)CC2)=C1 BCDAOQHGDOADCE-UHFFFAOYSA-N 0.000 description 1
- FDWYICPUJTUMEF-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[benzyl(methyl)carbamoyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C=1C=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=CC=1C(=O)N(C)CC1=CC=CC=C1 FDWYICPUJTUMEF-UHFFFAOYSA-N 0.000 description 1
- NJOKYFXDQQUNGP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[benzyl-(3-ethoxy-3-oxopropyl)carbamoyl]phenyl]-3-sulfanylpentanoic acid Chemical compound C=1C=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=CC=1C(=O)N(CCC(=O)OCC)CC1=CC=CC=C1 NJOKYFXDQQUNGP-UHFFFAOYSA-N 0.000 description 1
- JVBSMEFEAVVQAU-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[3-[cyanomethyl(methyl)sulfamoyl]phenyl]-3-sulfanylpentanoic acid Chemical compound N#CCN(C)S(=O)(=O)C1=CC=CC(CCC(S)C(CC=2C=NC(N)=CC=2)C(O)=O)=C1 JVBSMEFEAVVQAU-UHFFFAOYSA-N 0.000 description 1
- NGNVPYLKGAGWRH-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-[4-(cyanomethyl)phenyl]-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=C(CC#N)C=C1 NGNVPYLKGAGWRH-UHFFFAOYSA-N 0.000 description 1
- RDVCJDNLIKRSEP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-naphthalen-1-yl-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC2=CC=CC=C12 RDVCJDNLIKRSEP-UHFFFAOYSA-N 0.000 description 1
- YOYBVJFMVQXHLT-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-pyridin-2-yl-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC=N1 YOYBVJFMVQXHLT-UHFFFAOYSA-N 0.000 description 1
- AKECKOILXKVBNA-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-5-pyridin-3-yl-3-sulfanylpentanoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CN=C1 AKECKOILXKVBNA-UHFFFAOYSA-N 0.000 description 1
- AKPKWZRKZOAAAZ-UHFFFAOYSA-N 2-[2-(diaminomethylideneamino)ethylsulfanylmethyl]-3-sulfanylpropanoic acid Chemical compound NC(N)=NCCSCC(CS)C(O)=O AKPKWZRKZOAAAZ-UHFFFAOYSA-N 0.000 description 1
- KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical compound OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 1
- CEXQBKWRIRIYNO-UHFFFAOYSA-N 3-[5-(6-aminopyridin-3-yl)-4-carboxy-3-sulfanylpentyl]benzoic acid Chemical compound C1=NC(N)=CC=C1CC(C(O)=O)C(S)CCC1=CC=CC(C(O)=O)=C1 CEXQBKWRIRIYNO-UHFFFAOYSA-N 0.000 description 1
- XDPCNPCKDGQBAN-UHFFFAOYSA-N 3-hydroxytetrahydrofuran Chemical compound OC1CCOC1 XDPCNPCKDGQBAN-UHFFFAOYSA-N 0.000 description 1
- QGCCNWSXJHGUNL-UHFFFAOYSA-N 3-iodo-benzyl alcohol Chemical compound OCC1=CC=CC(I)=C1 QGCCNWSXJHGUNL-UHFFFAOYSA-N 0.000 description 1
- KVBWBCRPWVKFQT-UHFFFAOYSA-N 3-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(I)=C1 KVBWBCRPWVKFQT-UHFFFAOYSA-N 0.000 description 1
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 description 1
- BLYPSHVDSAPASP-UHFFFAOYSA-N 3-pyridin-2-ylpropanal Chemical compound O=CCCC1=CC=CC=N1 BLYPSHVDSAPASP-UHFFFAOYSA-N 0.000 description 1
- POXFXTSTVWDWIR-UHFFFAOYSA-N 4-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(I)C=C1 POXFXTSTVWDWIR-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010062506 Heparin-induced thrombocytopenia Diseases 0.000 description 1
- 208000033892 Hyperhomocysteinemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 208000004221 Multiple Trauma Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 108050008996 P2Y purinoceptor 1 Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 102000029301 Protein S Human genes 0.000 description 1
- 108010066124 Protein S Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038563 Reocclusion Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102000003938 Thromboxane Receptors Human genes 0.000 description 1
- 108090000300 Thromboxane Receptors Proteins 0.000 description 1
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 1
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003927 aminopyridines Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000003698 antivitamin K Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000015572 biosynthetic process Effects 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000013130 cardiovascular surgery Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000005796 circulatory shock Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960002768 dipyridamole Drugs 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000208 fibrin degradation product Substances 0.000 description 1
- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960001318 fondaparinux Drugs 0.000 description 1
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- VKVCLXDFOQQABP-BYPYZUCNSA-N guanidinoethylmercaptosuccinic acid Chemical compound NC(=N)NCCS[C@H](C(O)=O)CC(O)=O VKVCLXDFOQQABP-BYPYZUCNSA-N 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000002634 heparin fragment Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003225 hyperhomocysteinemia Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000002406 microsurgery Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- KGTZKKRPJASCAM-UHFFFAOYSA-N n-[3-(3,6-dichlorocarbazol-9-yl)-2-hydroxypropyl]-n,4-dimethylbenzenesulfonamide Chemical compound C12=CC=C(Cl)C=C2C2=CC(Cl)=CC=C2N1CC(O)CN(C)S(=O)(=O)C1=CC=C(C)C=C1 KGTZKKRPJASCAM-UHFFFAOYSA-N 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 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
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 230000033885 plasminogen activation Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 238000007395 thrombosis prophylaxis Methods 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
Classifications
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- 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
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201837 | 2002-06-14 | ||
| SE0201837A SE0201837D0 (sv) | 2002-06-14 | 2002-06-14 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2289297T3 true ES2289297T3 (es) | 2008-02-01 |
Family
ID=20288202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03730987T Expired - Lifetime ES2289297T3 (es) | 2002-06-14 | 2003-06-10 | Acido 3-mercaptopentanoico 2,5-disustituido. |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US7572817B2 (https=) |
| EP (1) | EP1532111B1 (https=) |
| JP (1) | JP2005533064A (https=) |
| KR (1) | KR20050010051A (https=) |
| CN (1) | CN100415719C (https=) |
| AR (1) | AR040240A1 (https=) |
| AT (1) | ATE369342T1 (https=) |
| AU (1) | AU2003241260B2 (https=) |
| BR (1) | BR0311384A (https=) |
| CA (1) | CA2488606A1 (https=) |
| CY (1) | CY1107753T1 (https=) |
| DE (1) | DE60315471T2 (https=) |
| DK (1) | DK1532111T3 (https=) |
| ES (1) | ES2289297T3 (https=) |
| IS (1) | IS7609A (https=) |
| MX (1) | MXPA04012604A (https=) |
| MY (1) | MY160429A (https=) |
| NO (1) | NO20045051L (https=) |
| NZ (1) | NZ536814A (https=) |
| PL (1) | PL373883A1 (https=) |
| PT (1) | PT1532111E (https=) |
| RU (1) | RU2365583C2 (https=) |
| SA (1) | SA03240142B1 (https=) |
| SE (1) | SE0201837D0 (https=) |
| TW (1) | TW200401766A (https=) |
| UA (1) | UA78042C2 (https=) |
| WO (1) | WO2003106420A1 (https=) |
| ZA (1) | ZA200409955B (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7276497B2 (en) * | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
| GB0403864D0 (en) * | 2004-02-20 | 2004-03-24 | Ucl Ventures | Modulator |
| CA2600869A1 (en) | 2005-03-18 | 2006-09-28 | The Regents Of The University Of California | Compounds having activity in correcting mutant-cftr processing and uses thereof |
| NZ592764A (en) | 2008-10-29 | 2012-08-31 | Taisho Pharmaceutical Co Ltd | Compound having tafia inhibitory activity |
| AP2011005795A0 (en) | 2009-02-13 | 2011-08-31 | Boehringer Ingelheim Int | SGLT-2 inhibitor for treating type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance or hyperglycemia. |
| HRP20190101T1 (hr) | 2013-04-05 | 2019-03-08 | Boehringer Ingelheim International Gmbh | Terapeutske uporabe empagliflozina |
| US20140303097A1 (en) | 2013-04-05 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| CA2812519A1 (en) | 2013-04-05 | 2014-10-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| FI4000608T3 (fi) | 2013-04-18 | 2026-01-21 | Boehringer Ingelheim Int | Farmaseuttinen koostumus, menetelmä hoitamiseksi ja sen käyttöjä |
| CA2914533A1 (en) | 2013-06-10 | 2014-12-18 | Sanofi | Macrocyclic urea derivatives as inhibitors of tafia, their preparation and their use as pharmaceuticals |
| KR20250097990A (ko) | 2016-11-10 | 2025-06-30 | 베링거 인겔하임 인터내셔날 게엠베하 | 약제학적 조성물, 치료 방법 및 이의 용도 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000066577A2 (en) * | 1999-04-29 | 2000-11-09 | Allergan Sales, Inc. | Brigded cycloalkanes as thromboxane ligands without blood clotting effects |
| SE9901573D0 (sv) * | 1999-05-03 | 1999-05-03 | Astra Ab | New compounds |
-
2002
- 2002-06-14 SE SE0201837A patent/SE0201837D0/xx unknown
-
2003
- 2003-06-02 AR ARP030101959A patent/AR040240A1/es unknown
- 2003-06-08 SA SA03240142A patent/SA03240142B1/ar unknown
- 2003-06-10 CN CNB038138409A patent/CN100415719C/zh not_active Expired - Fee Related
- 2003-06-10 ES ES03730987T patent/ES2289297T3/es not_active Expired - Lifetime
- 2003-06-10 KR KR10-2004-7020285A patent/KR20050010051A/ko not_active Ceased
- 2003-06-10 AT AT03730987T patent/ATE369342T1/de not_active IP Right Cessation
- 2003-06-10 PT PT03730987T patent/PT1532111E/pt unknown
- 2003-06-10 PL PL03373883A patent/PL373883A1/xx not_active Application Discontinuation
- 2003-06-10 EP EP03730987A patent/EP1532111B1/en not_active Expired - Lifetime
- 2003-06-10 AU AU2003241260A patent/AU2003241260B2/en not_active Ceased
- 2003-06-10 US US10/517,713 patent/US7572817B2/en not_active Expired - Fee Related
- 2003-06-10 DE DE60315471T patent/DE60315471T2/de not_active Expired - Fee Related
- 2003-06-10 RU RU2004134563/04A patent/RU2365583C2/ru not_active IP Right Cessation
- 2003-06-10 NZ NZ536814A patent/NZ536814A/en unknown
- 2003-06-10 MX MXPA04012604A patent/MXPA04012604A/es active IP Right Grant
- 2003-06-10 JP JP2004513253A patent/JP2005533064A/ja not_active Withdrawn
- 2003-06-10 DK DK03730987T patent/DK1532111T3/da active
- 2003-06-10 BR BR0311384-1A patent/BR0311384A/pt not_active IP Right Cessation
- 2003-06-10 CA CA002488606A patent/CA2488606A1/en not_active Abandoned
- 2003-06-10 WO PCT/SE2003/000970 patent/WO2003106420A1/en not_active Ceased
- 2003-06-12 TW TW092115988A patent/TW200401766A/zh unknown
- 2003-06-12 MY MYPI20032192A patent/MY160429A/en unknown
- 2003-10-06 UA UA20041109447A patent/UA78042C2/uk unknown
-
2004
- 2004-11-19 NO NO20045051A patent/NO20045051L/no not_active Application Discontinuation
- 2004-12-08 ZA ZA200409955A patent/ZA200409955B/en unknown
- 2004-12-22 IS IS7609A patent/IS7609A/is unknown
-
2007
- 2007-10-08 CY CY20071101274T patent/CY1107753T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2636050C2 (ru) | Замещенные пирролидины в качестве ингибиторов фактора xia для лечения тромбоэмболических заболеваний | |
| KR100416111B1 (ko) | 아미딘 화합물 | |
| JP4256065B2 (ja) | スルホニル誘導体 | |
| ES2289297T3 (es) | Acido 3-mercaptopentanoico 2,5-disustituido. | |
| EP2121612B1 (en) | Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals | |
| JPWO1999016747A1 (ja) | スルホニル誘導体 | |
| US7449457B2 (en) | Substituted heterocyclic carboxamides with antithrombotic activity | |
| JP7566870B2 (ja) | 酵素阻害剤 | |
| JP5778133B2 (ja) | シクロプロパンカルボン酸誘導体 | |
| PL200932B1 (pl) | Nowe związki, środek farmaceutyczny i zastosowanie nowych związków | |
| HK1077296B (en) | 2,5-disubstituted 3-mercaptopentanoic acid | |
| MXPA06000989A (es) | Derivados de nicotinamida utiles como inhibidores de pde4. | |
| JP2008546684A (ja) | トロンビン阻害性２−オキソ−１，２，５，６−テトラヒドロピリジン誘導体 | |
| EP1655296A1 (en) | Thrombin inhibitors | |
| KR19990015206A (ko) | 선택적 트롬빈 억제활성을 갖는 치환된 방향족 유도체 | |
| KR20070020400A (ko) | 트롬빈 억제제로서 유용한 신규한 5,6-디히드로피리딘-2-온화합물 |