NO300778B1 - Pseudopeptider, anvendelse derav, samt farmasöytiske preparater inneholdende slike - Google Patents
Pseudopeptider, anvendelse derav, samt farmasöytiske preparater inneholdende slike Download PDFInfo
- Publication number
- NO300778B1 NO300778B1 NO930830A NO930830A NO300778B1 NO 300778 B1 NO300778 B1 NO 300778B1 NO 930830 A NO930830 A NO 930830A NO 930830 A NO930830 A NO 930830A NO 300778 B1 NO300778 B1 NO 300778B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- acid
- denotes
- formula
- group
- Prior art date
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
- 150000003839 salts Chemical group 0.000 claims abstract description 10
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 8
- 230000001154 acute effect Effects 0.000 claims abstract description 5
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- -1 1-adamantyl Chemical group 0.000 claims description 13
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 8
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 5
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- OPSRUAAFZJIVQO-INIZCTEOSA-N (3s)-7-[(4-carbamimidoylbenzoyl)amino]-3-(3-methylbutanoylamino)heptanoic acid Chemical compound CC(C)CC(=O)N[C@H](CC(O)=O)CCCCNC(=O)C1=CC=C(C(N)=N)C=C1 OPSRUAAFZJIVQO-INIZCTEOSA-N 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- ILTAUWVOPNHLBE-DWBCTQMISA-N (3S)-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]-3-(3-methylbutanoylamino)hexanoic acid (3S)-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]-3-[(4-methylphenyl)sulfonylamino]hexanoic acid Chemical compound CC(CC(=O)N[C@H](CC(=O)O)CCCNC(CC1=CC=C(C=C1)C(N)=N)=O)C.S(=O)(=O)(C1=CC=C(C)C=C1)N[C@H](CC(=O)O)CCCNC(CC1=CC=C(C=C1)C(N)=N)=O ILTAUWVOPNHLBE-DWBCTQMISA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- 150000001875 compounds Chemical class 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- 239000000047 product Substances 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 17
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 17
- 108010049003 Fibrinogen Proteins 0.000 description 16
- 102000008946 Fibrinogen Human genes 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 229940012952 fibrinogen Drugs 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 210000001772 blood platelet Anatomy 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 9
- 150000004702 methyl esters Chemical class 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- UZHFJNQOZVEGEL-UHFFFAOYSA-N 2-[4-[(z)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenyl]acetic acid Chemical compound CC(C)(C)OC(=O)NC(=N)C1=CC=C(CC(O)=O)C=C1 UZHFJNQOZVEGEL-UHFFFAOYSA-N 0.000 description 7
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 7
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 4
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 4
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 4
- 108010035030 Platelet Membrane Glycoprotein IIb Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- XQUJDYKAECREGU-IVJSWOQWSA-N (3s)-3-[3-(1-adamantyl)propanoylamino]-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]hexanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1CC(=O)NCCC[C@@H](CC(O)=O)NC(=O)CCC1(C2)CC(C3)CC2CC3C1 XQUJDYKAECREGU-IVJSWOQWSA-N 0.000 description 2
- NAHSXOFCCYXMHP-RRNJLGJUSA-N (3s)-3-[[2-(1-adamantyl)acetyl]amino]-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]hexanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1CC(=O)NCCC[C@@H](CC(O)=O)NC(=O)CC1(C2)CC(C3)CC2CC3C1 NAHSXOFCCYXMHP-RRNJLGJUSA-N 0.000 description 2
- MDAJFZIQBMXEKL-INIZCTEOSA-N (3s)-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]-3-(3-methylbutanoylamino)hexanoic acid Chemical compound CC(C)CC(=O)N[C@H](CC(O)=O)CCCNC(=O)CC1=CC=C(C(N)=N)C=C1 MDAJFZIQBMXEKL-INIZCTEOSA-N 0.000 description 2
- QMRDCHKQISKMJS-SFHVURJKSA-N (3s)-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]-3-[(4-methylphenyl)sulfonylamino]hexanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](CC(O)=O)CCCNC(=O)CC1=CC=C(C(N)=N)C=C1 QMRDCHKQISKMJS-SFHVURJKSA-N 0.000 description 2
- OJOFMLDBXPDXLQ-SECBINFHSA-N (4r)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-SECBINFHSA-N 0.000 description 2
- CIRMRFWAZHFSPK-VIFPVBQESA-N (4s)-5-azido-4-[tert-butyl(dimethyl)silyl]oxypentanoic acid Chemical compound CC(C)(C)[Si](C)(C)O[C@@H](CCC(O)=O)CN=[N+]=[N-] CIRMRFWAZHFSPK-VIFPVBQESA-N 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- KBDLTYNZHQRMQC-UHFFFAOYSA-N 2-(4-methoxyphenyl)propanoic acid Chemical compound COC1=CC=C(C(C)C(O)=O)C=C1 KBDLTYNZHQRMQC-UHFFFAOYSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- CBLWJKHTKYGZTI-UHFFFAOYSA-N 4-[n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]benzoic acid Chemical compound CC(C)(C)OC(=O)\N=C(/N)C1=CC=C(C(O)=O)C=C1 CBLWJKHTKYGZTI-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- SCCPDJAQCXWPTF-VKHMYHEASA-N Gly-Asp Chemical compound NCC(=O)N[C@H](C(O)=O)CC(O)=O SCCPDJAQCXWPTF-VKHMYHEASA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 102100035140 Vitronectin Human genes 0.000 description 2
- 108010031318 Vitronectin Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
- UYNBZKXNRSJYAW-ZOWNYOTGSA-N methyl (3s)-3-amino-6-(phenylmethoxycarbonylamino)hexanoate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC(=O)C[C@@H](N)CCCNC(=O)OCC1=CC=CC=C1 UYNBZKXNRSJYAW-ZOWNYOTGSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- QYYCZJUFHDLLOJ-AWEZNQCLSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCNC(=O)OCC1=CC=CC=C1 QYYCZJUFHDLLOJ-AWEZNQCLSA-N 0.000 description 1
- BDHUTRNYBGWPBL-HNNXBMFYSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-(phenylmethoxycarbonylamino)hexanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCCNC(=O)OCC1=CC=CC=C1 BDHUTRNYBGWPBL-HNNXBMFYSA-N 0.000 description 1
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
- STSKWZSBFZRSGP-GYDGUXFESA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-6-amino-2-[[(2s)-2-[[2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]acetyl]amino]propanoyl]amino]he Chemical group C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)C1=CN=CN1 STSKWZSBFZRSGP-GYDGUXFESA-N 0.000 description 1
- ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-N 0.000 description 1
- XHKGUOUJRWEKRN-LWOIVNDQSA-N (3s)-3-[3-(1-adamantyl)propanoylamino]-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C(=N)N)=CC=C1CC(=O)NCCC[C@@H](CC(O)=O)NC(=O)CCC1(C2)CC(C3)CC2CC3C1 XHKGUOUJRWEKRN-LWOIVNDQSA-N 0.000 description 1
- UTLHJKKATBHFRF-FSCUCZSOSA-N (3s)-3-[[2-(1-adamantyl)acetyl]amino]-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C(=N)N)=CC=C1CC(=O)NCCC[C@@H](CC(O)=O)NC(=O)CC1(C2)CC(C3)CC2CC3C1 UTLHJKKATBHFRF-FSCUCZSOSA-N 0.000 description 1
- VZNLBPPMLYPGGQ-NTISSMGPSA-N (3s)-6-[[2-(4-carbamimidoylphenyl)acetyl]amino]-3-(3-methylbutanoylamino)hexanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC(C)CC(=O)N[C@H](CC(O)=O)CCCNC(=O)CC1=CC=C(C(N)=N)C=C1 VZNLBPPMLYPGGQ-NTISSMGPSA-N 0.000 description 1
- FGXYYCANBMNLKB-NTISSMGPSA-N (3s)-7-[(4-carbamimidoylbenzoyl)amino]-3-(3-methylbutanoylamino)heptanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC(C)CC(=O)N[C@H](CC(O)=O)CCCCNC(=O)C1=CC=C(C(N)=N)C=C1 FGXYYCANBMNLKB-NTISSMGPSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- SSGFEOFDJDCDCI-UHFFFAOYSA-N 2-(4-carbamimidoylphenyl)acetic acid Chemical compound NC(=N)C1=CC=C(CC(O)=O)C=C1 SSGFEOFDJDCDCI-UHFFFAOYSA-N 0.000 description 1
- SXSSVXAEIXMJIJ-UHFFFAOYSA-N 2-(4-methoxyphenyl)ethanesulfonyl chloride Chemical compound COC1=CC=C(CCS(Cl)(=O)=O)C=C1 SXSSVXAEIXMJIJ-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- MQLZRIWOJRILDI-UHFFFAOYSA-N 3-(1-adamantyl)propanoic acid Chemical compound C1C(C2)CC3CC2CC1(CCC(=O)O)C3 MQLZRIWOJRILDI-UHFFFAOYSA-N 0.000 description 1
- FIUFLISGGHNPSM-UHFFFAOYSA-N 3-(4-methoxyphenyl)propanoic acid Chemical compound COC1=CC=C(CCC(O)=O)C=C1 FIUFLISGGHNPSM-UHFFFAOYSA-N 0.000 description 1
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 1
- 102000007347 Apyrase Human genes 0.000 description 1
- 108010007730 Apyrase Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- OQWVYFPNWPBDFB-GOTSBHOMSA-N CC(C)(C)OC(=O)C[C@H](C[C@@H](CNC(=O)CC1=CC=C(C=C1)C(=N)NC(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)N Chemical compound CC(C)(C)OC(=O)C[C@H](C[C@@H](CNC(=O)CC1=CC=C(C=C1)C(=N)NC(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)N OQWVYFPNWPBDFB-GOTSBHOMSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- TVZNFYXAPXOARC-UHFFFAOYSA-N Dl-norleucine methyl ester Chemical compound CCCCC(N)C(=O)OC TVZNFYXAPXOARC-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010038563 Reocclusion Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000006241 alcohol protecting group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- JRZBPELLUMBLQU-UHFFFAOYSA-N carbonazidic acid Chemical compound OC(=O)N=[N+]=[N-] JRZBPELLUMBLQU-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- JJGFQWYONXOBQG-PPHPATTJSA-N methyl (3s)-6-amino-3-(3-methylbutanoylamino)hexanoate;hydrochloride Chemical compound Cl.COC(=O)C[C@H](CCCN)NC(=O)CC(C)C JJGFQWYONXOBQG-PPHPATTJSA-N 0.000 description 1
- WIJGPWLKPNTYDO-YDALLXLXSA-N methyl (3s)-6-amino-3-[(4-methylphenyl)sulfonylamino]hexanoate;hydrochloride Chemical compound Cl.COC(=O)C[C@H](CCCN)NS(=O)(=O)C1=CC=C(C)C=C1 WIJGPWLKPNTYDO-YDALLXLXSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000005602 pentanoic acid derivatives Chemical class 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- WWJZWCUNLNYYAU-UHFFFAOYSA-N temephos Chemical compound C1=CC(OP(=S)(OC)OC)=CC=C1SC1=CC=C(OP(=S)(OC)OC)C=C1 WWJZWCUNLNYYAU-UHFFFAOYSA-N 0.000 description 1
- WLHAQWFNHFRWSF-KYJUHHDHSA-N tert-butyl (3S,5S)-5-[tert-butyl(dimethyl)silyl]oxy-6-[[2-[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenyl]acetyl]amino]-3-(phenylmethoxycarbonylamino)hexanoate Chemical compound CC(C)(C)OC(=O)C[C@H](C[C@@H](CNC(=O)CC1=CC=C(C=C1)C(=N)NC(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)NC(=O)OCC2=CC=CC=C2 WLHAQWFNHFRWSF-KYJUHHDHSA-N 0.000 description 1
- SHUIJNGFNADJPS-PMACEKPBSA-N tert-butyl (3S,5S)-6-azido-5-[tert-butyl(dimethyl)silyl]oxy-3-(phenylmethoxycarbonylamino)hexanoate Chemical compound N#[N+][N-]C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@@H](CC(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 SHUIJNGFNADJPS-PMACEKPBSA-N 0.000 description 1
- YROVKSCEXQTHTJ-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroacetate Chemical compound CC(C)(C)OC(=O)C(Cl)(Cl)Cl YROVKSCEXQTHTJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WLUUTGIJNRNHRF-UHFFFAOYSA-N tert-butyl heptanoate Chemical compound CCCCCCC(=O)OC(C)(C)C WLUUTGIJNRNHRF-UHFFFAOYSA-N 0.000 description 1
- DANUJARGWMPVQX-UHFFFAOYSA-N tert-butyl hexanoate Chemical class CCCCCC(=O)OC(C)(C)C DANUJARGWMPVQX-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with 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
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Pyrane Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4207544 | 1992-03-10 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO930830D0 NO930830D0 (no) | 1993-03-08 |
| NO930830L NO930830L (no) | 1993-09-13 |
| NO300778B1 true NO300778B1 (no) | 1997-07-21 |
Family
ID=6453662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO930830A NO300778B1 (no) | 1992-03-10 | 1993-03-08 | Pseudopeptider, anvendelse derav, samt farmasöytiske preparater inneholdende slike |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US5561112A (zh) |
| EP (1) | EP0560730B1 (zh) |
| JP (1) | JP2860222B2 (zh) |
| KR (1) | KR930019690A (zh) |
| CN (1) | CN1076200A (zh) |
| AT (1) | ATE142618T1 (zh) |
| AU (1) | AU659281B2 (zh) |
| CA (1) | CA2091292A1 (zh) |
| CZ (1) | CZ36193A3 (zh) |
| DE (1) | DE69304573T2 (zh) |
| DK (1) | DK0560730T3 (zh) |
| ES (1) | ES2090934T3 (zh) |
| FI (1) | FI931023A (zh) |
| GR (1) | GR3021030T3 (zh) |
| HU (2) | HUT63609A (zh) |
| IL (1) | IL104972A (zh) |
| MX (1) | MX9301298A (zh) |
| MY (1) | MY109060A (zh) |
| NO (1) | NO300778B1 (zh) |
| NZ (1) | NZ247084A (zh) |
| PH (1) | PH30893A (zh) |
| RU (1) | RU2106356C1 (zh) |
| SG (1) | SG47059A1 (zh) |
| SK (1) | SK17093A3 (zh) |
| TW (1) | TW256828B (zh) |
| ZA (1) | ZA931724B (zh) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
| GB9406143D0 (en) * | 1993-03-29 | 1994-05-18 | Zeneca Ltd | Heterocyclic derivatives |
| AU692439B2 (en) * | 1993-03-29 | 1998-06-11 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
| DE4310643A1 (de) * | 1993-04-01 | 1994-10-06 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| US5811398A (en) * | 1995-04-11 | 1998-09-22 | G. D. Searle & Co. | Platelet aggregation inhibitors containing C-terminal aminergic side chain amino acid residues |
| DE69717268T2 (de) * | 1996-02-22 | 2003-09-04 | Bristol Myers Squibb Pharma Co | M-amidinophenyl-analoga als faktor-xa-inhibitoren |
| US5942544A (en) * | 1996-02-22 | 1999-08-24 | Dupont Pharmaceuticals Company | α-branched anilines, toluenes, and analogs thereof as factor Xa inhibitors |
| JP2005526023A (ja) * | 2002-01-28 | 2005-09-02 | ノバルティス アクチエンゲゼルシャフト | β−ホモリジンコンジュゲートおよび輸送エンハンサーとしてのそれらの使用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4578079A (en) * | 1982-08-04 | 1986-03-25 | La Jolla Cancer Research Foundation | Tetrapeptide |
| US4879313A (en) * | 1988-07-20 | 1989-11-07 | Mosanto Company | Novel platelet-aggregation inhibitors |
| US5039805A (en) * | 1988-12-08 | 1991-08-13 | Hoffmann-La Roche Inc. | Novel benzoic and phenylacetic acid derivatives |
| US5273982A (en) * | 1990-03-09 | 1993-12-28 | Hoffmann-La Roche Inc. | Acetic acid derivatives |
| CA2037153A1 (en) * | 1990-03-09 | 1991-09-10 | Leo Alig | Acetic acid derivatives |
| US5354738A (en) * | 1992-09-04 | 1994-10-11 | G. D. Searle & Co. | Platelet aggregation inhibitors |
-
1993
- 1993-02-24 HU HU9300501A patent/HUT63609A/hu unknown
- 1993-03-08 FI FI931023A patent/FI931023A/fi not_active Application Discontinuation
- 1993-03-08 NZ NZ247084A patent/NZ247084A/en unknown
- 1993-03-08 PH PH45820A patent/PH30893A/en unknown
- 1993-03-08 DE DE69304573T patent/DE69304573T2/de not_active Expired - Fee Related
- 1993-03-08 SK SK17093A patent/SK17093A3/sk unknown
- 1993-03-08 MY MYPI93000412A patent/MY109060A/en unknown
- 1993-03-08 EP EP93810172A patent/EP0560730B1/en not_active Expired - Lifetime
- 1993-03-08 ES ES93810172T patent/ES2090934T3/es not_active Expired - Lifetime
- 1993-03-08 SG SG1996004849A patent/SG47059A1/en unknown
- 1993-03-08 CZ CZ93361A patent/CZ36193A3/cs unknown
- 1993-03-08 NO NO930830A patent/NO300778B1/no unknown
- 1993-03-08 DK DK93810172.2T patent/DK0560730T3/da active
- 1993-03-08 IL IL104972A patent/IL104972A/en not_active IP Right Cessation
- 1993-03-08 AT AT93810172T patent/ATE142618T1/de not_active IP Right Cessation
- 1993-03-09 RU RU93004781A patent/RU2106356C1/ru active
- 1993-03-09 CN CN93102483A patent/CN1076200A/zh active Pending
- 1993-03-09 JP JP5047780A patent/JP2860222B2/ja not_active Expired - Lifetime
- 1993-03-09 CA CA002091292A patent/CA2091292A1/en not_active Abandoned
- 1993-03-09 MX MX9301298A patent/MX9301298A/es not_active IP Right Cessation
- 1993-03-09 AU AU34069/93A patent/AU659281B2/en not_active Ceased
- 1993-03-09 KR KR1019930003492A patent/KR930019690A/ko not_active Application Discontinuation
- 1993-03-10 ZA ZA931724A patent/ZA931724B/xx unknown
- 1993-03-11 TW TW082101802A patent/TW256828B/zh active
-
1994
- 1994-03-01 US US08/204,836 patent/US5561112A/en not_active Expired - Fee Related
-
1995
- 1995-05-30 HU HU95P/P00143P patent/HU210878A9/hu unknown
-
1996
- 1996-09-12 GR GR960402384T patent/GR3021030T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5430024A (en) | Peptides bearing N-terminal amidino moieties and their use as inhibitors of platelet aggregation | |
| AU643036B2 (en) | Dipeptide derivatives | |
| AU648751B2 (en) | Novel aminobenzoates | |
| RU2024549C1 (ru) | Производные глицина или их физиологически приемлемые соли, обладающие способностью тормозить связывание фибриногена у фибриногенного рецептора тромбоцитов | |
| US5552431A (en) | Peptide mimetic compounds useful as platelet aggregation inhibitors | |
| KR100223662B1 (ko) | 자동 금전 출납기를 사용하여 송금된 돈을 지급하는 전자 송금 시스템 및 방법 | |
| US5399585A (en) | Carboxamides and sulfonamides compounds which have useful pharmaceutical utility | |
| IL97401A (en) | History of Acetic Acids Preparation and Pharmaceutical Preparations Containing Them | |
| NO300778B1 (no) | Pseudopeptider, anvendelse derav, samt farmasöytiske preparater inneholdende slike | |
| US6235717B1 (en) | Pharmaceutical compounds | |
| US5344837A (en) | Platelet aggregation inhibitors | |
| AU3819999A (en) | Certain thiol inhibitors of endothelin-converting enzyme | |
| US4985407A (en) | Dipeptide compounds, processes for their preparation and compositions containing them | |
| US5798370A (en) | Platelet aggregation inhibitors | |
| US6268380B1 (en) | Urea derivatives useful as platelet aggregation inhibitors | |
| WO1994020457A1 (en) | N-acyl beta amino acid derivatives useful as platelet aggregation inhibitors | |
| EP1864995B1 (en) | Beta-lactamic rgd cyclopeptides containing gamma turns | |
| US5625093A (en) | Substituted β-amino acid derivatives useful as platelet aggregation inhibitors | |
| KR100798560B1 (ko) | 페린도프릴 및 이들의 약제학적 허용 염의 합성을 위한방법 | |
| US20070037845A1 (en) | Peptido-mimetic compounds containing rgd sequence useful as integrin inhibitors, and intermediates thereof | |
| US5811398A (en) | Platelet aggregation inhibitors containing C-terminal aminergic side chain amino acid residues | |
| JPH0797393A (ja) | 新規エンドセリン拮抗性ペプチド |