| 摘要 |
Use of acylated 4-(amidino or guanidino)benzylamine derivatives (I) for inhibition of plasma kallikrein (PK). Use of acylated 4-(amidino or guanidino)benzylamine derivatives of formula (I) for inhibition of plasma kallikrein (PK). P4-P3-P2-P1 (I) P4 : benzylsulfonyl, optionally substituted one or more times; P3 : natural or unnatural alpha -amino acid (aaa) or alpha -imino acid (aia) with D configuration, optionally substituted one or more times; P2 : natural or unnatural alpha -amino acid (aaa) or alpha -imino acid (aia) with L configuration, optionally substituted one or more times; P1 : 4-(amidino or guanidino)benzylamino group, optionally substituted one or more times. Independent claims are also included for the following: (1) (I) when (non-)covalently linked to a synthetic surface; (2) synthetic surface to which (I) is (non-)covalently bonded; and (3) instruments that contain the surface of (2). ACTIVITY : Anticoagulant; Thrombolytic; Cardiant; Cerebroprotective; Antianginal; Antibacterial; Immunosuppressive; Antiallergic; Antiarthritic. 3-(glutarylaminomethyl)-benzylsulfonyl-D-Cha-Pro-4-aminobenzylamine as trifluoroacetate (Cha = cyclohexylalanine) had inhibition constant (by the method of J. Med. Chem., 40 (1997) 3091) 0.044 MicroM for PK and below 0.001 MicroM for thrombin. MECHANISM OF ACTION : Inhibition of plasma kallikrein and other trypsin-like serine proteases, e.g. thrombin; activated factors Xa, XIIa, VIIa or IXa; urokinase; tryptase and plasmin; also serine proteases of the complement system. |
