New carboxylic acid compounds useful e.g. as antiinflammatory or antithrombotic agents

摘要

Carboxylic acid derivatives of formula A-B-C-D-E-Ra (I) and their tautomers, stereoisomers and salts are new. A = a 5-7 membered azacycloalkyl coupled to B via one of its C atoms, which is 1-substituted by Rb and optionally substituted on its C by 1-3 1-3C alkyl groups or A = 5-7 membered biazacycloalkyl where a methylene may be replaced by CO and which is coupled to B via the second N atom in the 3- or 4-position and is substituted as before; Rb = H, 1-3C alkyl, phenyl-(1-3C alkyl), 1-3C alkylcarbonyl, COCF3, 1-5C alkoxycarbonyl, phenyl-(1-3C alkoxycarbonyl) or CO-O-(CHR2)-O-CO-R1; R1 = 1-5C alkyl, 5-7C cycloalkyl, phenyl-(1-3C alkyl), 1-5C alkoxy, 5-7C cycloalkoxy or phenyl; R2 = H, 1-4C alkyl, 5-7C cycloalkyl or phenyl; B = a 5-7 membered azacycloalkylene which is coupled to A and C in the 1,3- or 1,4-position and is optionally substituted by 1-3 1-3C alkyl groups; C = -O-CO-, -CHR3-CO-, -CHR3-CH2-CO-, -CH2-CHR3-CO-, -CHR3-CO-NR3-, -CHR3-CH2-CO-NR3-, -CH2-CHR3-CO-NR3-, -CO-CHR3-CO-, -CO-CHR3-CO-NR3- or -O-CO-NR3-; R3 = H, 1-5C alkyl, phenyl-(1-3C alkyl) or phenyl; D = phenylene, cyclohexylene or 1,4-piperidinylene or 1,4-piperazinyl optionally substituted by R4 and in which a methylene group may be replaced by CO; E = -CO-, -(CHR3)n-CO-, -NR3-(CHR5)m-CO- or -O-CHR5-CO-; R5 = H, 1-5C alkyl, phenyl-(1-3C alkyl), phenyl, pyridyl or ethynyl; n = 1-3; m = 1 or 2; Ra = OH, 1-6C alkoxy, phenyl-(1-3C alkoxy), 3-9C cycloalkoxy (if the cycloalkyl group has 5-8C atoms it may be substituted by 1 or 2 1-3C alkyl groups), 5-8C cycloalkoxy (where the CH2 group in the 3- or 4-position may be replaced by an O atom or an NH group optionally substituted by 1-3C alkyl, phenyl-(1-3C alkyl), phenyl-(1-3C alkoxycarbonyl) or 2-6C alkanoyl and whose cycloalkyl ring may be substituted by 1 or 2 1-3C alkyl groups), 4-7C cycloalkenyloxy, 3-8C cycloalkyl-(1-3C alkoxy), 3-5C alkenyloxy, phenyl-(3-5C alkenyloxy), 3-5C alkynyloxy or phenyl-(3-5C alkynyloxy) provided that there is no bond to an O atom from a C atom that contains a double or triple bond; Ra may also be 8-10C bicycloalkoxy (optionally substituted by 1 or 2 1-3C alkyl groups), 1,3-dihydro-3-oxo-1-isobenzofuranyloxy, -O-(CR6R7)-O-CO-R8 or the side chain of a natural alpha -amino acid or one of its esters; R6 = H, 1-6C alkyl, 3-7C cycloalkyl or phenyl; R7 = H or 1-6C alkyl, R8 = 1-5C alkyl, 1-5C alkoxy, 5-7C cycloalkyl or 5-7C cycloalkyloxy. All the above phenyl and phenylene groups may be substituted by 1-3 F, Cl, Br, I, 1-3C alkyl, OH, 1-3C alkoxy, phenyl-(1-3C alkoxy) or NH2 groups.