New sugar-modified amidine and guanidine compounds, useful as competitive inhibitors of serine protease, e.g. for treating thrombosis

摘要

Amidine or guanidine derivatives (I) that include polyhydroxy (cyclo)alkyl groups, their tautomers, stereoisomers, salts and prodrugs. Amidine or guanidine derivatives of formula (I), which include polyhydroxy (cyclo)alkyl groups, their tautomers, stereoisomers, salts and prodrugs are new A-B-D-E-G-K-L (I) A = hydrogen, Me or H-(RA1)iA; RA1 = oxygen-containing heterocyclic residue; iA = 1-20 and if over 1, RA1 are same or different; J = one of the groups RB3-(CH-OH)mB-CH(O)-(CH-OH)lB-(CH-RB2)kB-CH(RB1)-, RB4-(CH-OH)mB-CH(O-)-(CH-OH)nB-CO-, RB4-(CH-OH)mB-CO-CH(O-)-(CH-OH)nB-CO-, or -O-CH2-CO-CH(OH)-(CH-OH)nB-CO-, or A and B together form one of four cyclic groups, or (N-acetyl)neuraminic acid residue, attached through carboxy; RB1 = hydrogen, hydroxymethyl or 1-4C alkyl; RB2 = hydrogen, amino, (acetyl)amino, fluoro or formylamino; RB3 = hydrogen, 1-4C alkyl, 1-4C alkoxymethyl, carboxy, fluoro, acetylamino or aminocarbonyl; RB4 = hydrogen, 1-4C alkyl, 1-4C alkoxymethyl, carboxy or formyl (optionally as acetal); RB5 = hydrogen, 1-4C alkyl, 1-4C alkoxymethyl or carboxy; kB = 0 or 1; lB = 0-3 but not 0 if A, RB1 and RB3 are all hydrogen and D = bond); mB = 0-4; nB = 0-3; D = bond or -N(RD1)-RD2-RD3-RD4-; RD1 = hydrogen or 1-4C alkyl; RD2 = bond or 1-4C alkyl; RD3 = any of 9 cyclic groups; RD4 = bond, 1-4C alkyl, carbonyl, sulfonyl or CH2CO; E = specified aminoalkyl residue; G = any of three 2-carbonyl-N-heterocyclic gropus linked through ring N and the carbonyl, or the group RG3-(CH2)qG-N(-)-CH(CO-)(CH2)rGRG4; qG and rG = 0-2; RG3 and RG4 = hydrogen, 1-6C alkyl, 3-8C cycloalkyl or aryl; K = -NH-(CH2)nK-QK; nK = 0-3; QK = 2-6C alkyl (optionally with up to two CH2 replaced by oxygen or sulfur) or is any of 9 specified heterocyclic residues; L = -C(=NH)-NHRL1 or -NH-C(=NH)-NHRL1; L1 = hydrogen, hydroxy, 1-6C alkoxy, phenyl(CH2)z-O-, 1-6C alkylcarbonyl, 1-6C alkoxycarbonyl or 1-3Calkylaryloxycarbonyl. The full definitions are given in the DEFINITIONS (Full Definitions) Field.