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ORGANIC COMPOUNDS WITH BIOLOGICAL ACTIVITY AS THROMBINIUM AND THEIR USE
专利权人:
CPI CREATIVE PHARMA INTERNATIONAL GMBH
发明人:
THUERK, MARCEL,SCHWIENHORST, ANDREAS
申请号:
AT09012354
公开号:
AT538843T
申请日:
2004.01.15
申请国别(地区):
AT
年份:
2012
代理人:
摘要:
Short peptides (I), optionally truncated at the C and/or N terminus, and their pharmaceutically acceptable salts are new. Peptides of formula (I) optionally truncated at the C and/or N terminus, and their pharmaceutically acceptable salts are new Y1(NH-X1-CO)-(NH-X2-CO)-(NH-X3-CO)-(NH-X4-CO)-(NH-X5-CO)-(NH-X6-CO)-Y2 (I) Y1 : hydrogen, methyl, acetyl or a 1-32C backbone; NH-X1-CO : a bond or the residue of, all D or L, Val, Ala, Leu, Ile, norleucine (Nle), Asn, Gln, Ser, Thr, Tyr, Arg, Lys, ornithine (Orn), Phe , dichloro-Phe, tetrahydronorharman-3-carboxylic acid (Nhm), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Iq3), 4-phenylpiperidine-4-carboxylic acid (Ppd), thienylalanine (Tea), phenylglycine (Phg), p-nitro-Phe, trans-4-aminomethyl-cyclohexane carboxylic acid (Tam) or trans-4-guanidinomethyl-cyclohexane carboxylic acid (Tgm); NH-X2-CO : a bond or the residue of, all D or L, Ala, Val, Leu, Ile, Nle, Ser, Thr, Tyr, Pro, citrulline (Cit), Arg, Lys, Orn, His, Glu, Asp, Trp, cyclohexylalanine (Cha) or cyclohexylglycine (Chg); NH-X3-CO : any amino acid (aa) residue, particularly L or D Cha or Chg; NH-X4-CO : small amino acid, especially L or D Pro or azetidine-2-carboxylic acid; NH-X5-CO : aromatic amino acid, especially D or L Phe or Tyr; NH-X6-CO : amino acid with basic sidechain, especially L or D Arg, Lys, Orn or homoArg; and Y2 : hydroxy, amino, hydrogen, 7-amido-4-methyl-coumarin, p-nitroanilide or a chain of 1-35 atoms. ACTIVITY : Anticoagulant; Thrombolytic; Cardiant; Cerebroprotective; Antiinflammatory; Cytostatic; Neuroprotective; Antiarteriosclerotic; Vasotropic. MECHANISM OF ACTION : Inhibition of thrombin. When tested for inhibition of the amidase activity of thrombin, the compound N-acetyl-D-Gln-D-His-L-cyclohexylalanyl-D-Pro-D-Tyr-L-Arg-amide gave 59% inhibition at 1 MicroM.
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