Patent TW-394760-B (TW)
Title: Novel Carboxamides, process for their preparation and pharmaceutical composition containing the same
Inventor: ACKERMANN JEAN
IPC: C07D413/14
Filed: 1994-08-23
Granted: 2000-06-21
Abstract: The novel carboxamides of the formula wherein A, E, G, L, M, R and Q have the significance given in the description, as well as hydrates or solvates thereof inhibit thrombin-induced platelet aggregation and fibrinogen coagulation in plasma. They can be manufactured starting from the corresponding acid and the corresponding amine H2NCH2Q. Carboxamides of the formula wherein E is hydrogen, G is H, lower-alkyl or (optionally bonded via lower-alkylene) COOH, coo-lower-alkyl, lower- alkanoyl, OH, lower-alkanoyloxy, lower-alkoxy, aryl-lower-alkoxy, CONH2, CONHCH2CH2OH, CONHOH, CONHOCH3, CONHO-benzyl, CONHSO2-lower-alkyl, NH2, NHCOO-lower-alkyl, NHCOO-lower-aralkyl, NHSO3H, (NHSO2 or NHSO3)- lower-alkyl, NH lower-alkanoyl, NHCOCOOH, NHCOCOO-lower-alkyl, NH-(3,4-dioxo-2-hydroxy-cyclobut-1-enyl), NH-[2-lower-(alkoxy or -alkenyloxy)-3, 4-dioxocyclobut-1-enyl], NHCOCH2C1, NHCO-lower-alkylene-O-(lower-alkyl or aryl), NHCOCH2[aryl, heteroaryl or-N(Het)], NHCOC(NOH)-lower-alkylene-COOH, NHSO2-N(Het), NHCO-(aryl, heteroaryl or heterocyclyl), NHPO3(R10, R20) or a group CO-N(Het), R10 and R20 are H, lower-alkyl or phenyl, M is H, lower-alkyl or-alkenyl, aryl, heteroaryl or cycloalkyl and L is H, lower-alkyl or (aryl or cycloalkyl)-lower-alkyl or M and L together with the atoms to which they are attached form  a group-N(Het) or E and G together form a methylene or carbonyl group and M is H, lower-alkyl or -alkenyl, aryl, heteroaryl, cycloalkyl or carboxy-lower-alkyl and L is H, lower-alkyl or (aryl or cycloalkyl)-lower-alkyl, A is H, alkyl, lower-aralkyl or a group of the formula: -C(O)R2 (A1), -S(O)2N(R3, R4)(A2) or, where group Q contains a hydroxy group R6 or R7 and/or where E and G together are CH2 or CO, then A can also be a group of the formula-S(O)2R5(A3), R2 is lower-alkyl, aryl, heteroaryl or cycloalkyl optionally bonded via lower-alkylene, carbo-lower-alkoxy bonded via lower-alkylene or-(O or S)-(aryl, heteroaryl or cycloalkyl) bonded via lower-alkylene, whereby a lower-alkylene group present in R2 can be substituted by hydroxy, amino or lower-alkanoylamino in the <alpha>-position to the carbonyl group to which R2 is bonded or R2 is halogen, carboxy, lower alkoxy, amino, mono-or di-lower-alkyl-amino or a group-N(Het) bonded via lower alkylene or R2 is a group -OR22 or -NHR22, R22 is lower-alkyl o raryl, heteroaryl or cycloalkyl optionally bonded via lower-alkylene or lower-aralkyl substituted in the lower-alkyl moiety by aryl, carbo-lower-alkoxy or COOH, R3 and R4 each independently are hydrogen, alkyl or aryl-lower-alkyl or together with the N atom to which they are attached form a group-N(Het), R5 is aryl, heteroaryl, heterocyclyl, alkyl or cyclo-alkyl, -N(Het) is N-bonded-N(CH2)4-9 optionally interrupted by O, S, NH or N-lower-alkyl and optionally substituted by up to 2 substituents from the group of lower-alkyl, OH, OXO, COOH, COO-lower-alkyl, CH2OOH and CH2O-benzyl, Q is a group of formula Q1 or Q2: T is CH2 or O, one of R6 and R7 is hydrogen or carbo-lower-alkoxy and the other if hydrogen, carbo-lower-alkoxy or hydroxy, and R is hydrogen or lower-alkyl, the term""lower"" denotes groups with up to 6 c atoms, ""aryl"" alone or in combination in ""lower aralkyl"" denotes phenyl or naphthyl optionally substituted by halogen, lower alkyl, lower alkoxy, OH phenyl, CF3, OCF3, cyclopentyl, CN, COOH, COOCH3, COOC2H5, CONH2 or tetrazolyl, ""heteroaryl"" denotes pyridyl, furyl, pyrimidinyl, indolyl, pyrazinyl, pyridazinyl, tetrazolyl, oxadiazolyl, quinolyl or imidazolyl, optionally substituted by oxo, lower-alkyl, halogen or amino, ""cycloalkyl"" contains 3 to 8 C atoms, and ""heterocyclyl"" denotes optionally lower-alkylated tetrahydroquinolyl or tetrahydropyridazinyl, as well as physiologically compatible salts thereof.