159675-85-1

A series of new trypsin-like serine protease inhibitors, 1, 2 and 7-23, containing amidinobenzene moiety was found to show potent LTB4-receptor affinity. Among them, compounds 1 and 2 were found to be LTB4 receptor antagonists based on an inhibition assay of human polymorphonuclear neutrophil (PMN) intracellular calcium mobilization induced by LTB4. Compounds 1 and 2, which satisfy the reported structural requirements for good oral activity, are expected to show a balanced dual mode of action, i.e., protease inhibitory activity and LTB4 receptor antagonist activity, in vivo.

Amidinophenol derivatives of the formula (I): STR1 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) STR2 in which STR3 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 tile 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.