| 摘要 |
Amidinophenol derivatives of the formula (I): (see formula I) wherein R1 and R2 are (i) H, (ii) C1-4 alkyl, (iii) C1-4 alkoxy, (iv) C2-5 acyl, (v) halogen, (vi) NO2, (vii) benzoyl, (viii) COOR4 (in which R4 is C1-3 alkyl); A is bond, C1-4 alkylene, -C(R5)=C(R6)- (in which R5 and R6 are H or C1-4 alkyl); R3 is (i) CON(R7)(R8), (ii) CON(R9)-CH(R7)(R8) or (iii) (see formula II) (in which R7 and R8 are (1) H, (2) phenyl, (3) C7-10 phenylalkyl, (4) pheny or C7-10 phenylalkyl substituted by 1 or 2 C1-4 alkyl) halogen or R11-COOR12 (in which R11 is bond, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene; R12 is H, C1-4 alkyl, C7-10 phenylalkyl, phenyl, allyl, propargyl), (5) C1-10 alkyl, (6) C2-10 alkenyl having 1 to 3 double bonds, (7) C2-10 alkynyl having 1 or 2 triple bonds, (8) R11a-COXR12 (in which R11a is (a) bond, (b) C1-8 alkylene, (c) C2-8 alkylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene, (d) C2-8 alkenylene, (e) C4-8 alkenylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene, (f) C2-8 alkynylene, (g)C4-8 alkynylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene; X is -O- or -NH-), (9) C1-4 alkyl substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one N atom, (10) C3-7 cycloalkyl); R9 is (1) H, (2) C1-8 alkyl, (3) C7-10 phenylalkyl, (4) C2-10 alkenyl having 1 to 3 double bonds, (5) C2-10 alkynyl having 1 or 2 triple bonds, (6) R11-COOR12. (7) C3-7 cycloalkyl; (see formula III) is 4-7 membered, mono-cyclic hetero ring containing 1 or 2 N atom; R10 is H, C7-10 phenylalkyl or COOR13 (in which R13 is H, C1-4 alkyl or C7-10 phenylalkyl)); with the proviso that (i) both R7 and R8 do not represent hydrogen at the same time, and (ii) when at least one group in R7, R8 and R9 represents the group containing t-butyl ester, the other groups do not represent the group containing carboxy; or an acid addition salt thereof, have inhibitory activities on PLA2 and on various proteases such as trypsin, plasmin, thrombin, kallikrein, especially trypsin, and are useful for the prevention and/or the treatment of various inflammatory diseases, allergic diseases, disseminated intravascular coagulation, pancreatitis, severity in pancreatitis and multiple organ failure.
|
