Substituted isoquinoline-3-carboxamides, their preparation and their use as pharmaceuticals

A compound of the formula Ia, or a physiologically active salt thereof:

• ##STR8## in which R.sup.1 is hydrogen or chlorine;
• R.sup.2 is hydrogen, (C.sub.1 -C.sub.8)-alkyl, (C.sub.1 -C.sub.8)-alkoxy, chlorine, trifluoromethyl, hydroxyl, benzyloxy, which is unsubstituted or substituted by a substituent selected from the group consisting of (C.sub.1 -C.sub.5)-alkyl, and (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• where
• x=0 or 1,
• f=an integer from 1 to 5, and
• g=an integer from 1 to (2f+1);
• R.sup.3 is hydrogen, (C.sub.1 -C.sub.8)-alkyl, (C.sub.1 -C.sub.8)-alkoxy, fluorine, chlorine, cyano, trifluoromethyl, hydroxyl, benzyloxy which is unsubstituted or substituted by a substituent selected from the group consisting of (C.sub.1 -C.sub.5)-alkyl and (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• in which x, f, and g are as defined above;
• and
• R.sup.4 and R.sup.5 independently are hydrogen, (C.sub.1 -C.sub.5)-alkyl, fluorine, chlorine, bromine, trifluoromethyl, cyano, (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• in which x, f, and g are as defined above.

A process for the preparation of a compound of the formula I:

• ##STR9## in which R.sup.1 is hydrogen or chlorine:
• R.sup.2 is hydrogen, (C.sub.1 -C.sub.8)-alkyl, (C.sub.1 -C.sub.8)-alkoxy, chlorine, trifluoromethyl, hydroxyl, benzyloxy which is unsubstituted or substituted by a substituent selected from the group consisting of (C.sub.1 -C.sub.5)-alkyl and (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• where
• x=0 or 1,
• f=an integer from 1 to 5, and
• g=an integer from 1 to (2f+1);
• R.sup.3 is hydrogen, (C.sub.1 -C.sub.8)-alkyl, (C.sub.1 -C.sub.8)-alkoxy, fluorine, chlorine, cyano, trifluoromethyl, hydroxyl, benzyloxy which is unsubstituted or substituted by a substituent selected from the group consisting of (C.sub.1 -C.sub.5)-alkyl and (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• in which x, f, and g are as defined above;
• and
• R.sup.4 and R.sup.5 independently are hydrogen, (C.sub.1 -C.sub.5)-alkyl, fluorine, chlorine, bromine, trifluoromethyl, cyano, (C.sub.1 -C.sub.5)-alkoxy, or fluoroalkoxy of the formula
• O--[CH.sub.2 ].sub.x --C.sub.f H.sub.(2f+1-g) F.sub.g
• in which x, f, and g are as defined above;
• which comprises
• I.i) reacting a quinoline-2-carboxylic acid of the formula II ##STR10## with an amino ester of the formula III:
• H.sub.2 N--CH.sub.2 --CO.sub.2 R (III)
• in which R is H, (C.sub.1 -C.sub.8)-alkyl, or benzyl;
• to give an amide ester of the formula IV:
• ##STR11## and I.ii) releasing the compound of the formula I:
• ##STR12## from its ester of the formula IV.