Quinoline and quinazoline derivatives inhibiting platelet-derived growth factor receptor autophosphorylation and pharmaceutical compositions containing the same

A quinoline derivative, or a pharmaceutically acceptable salt thereof,

• wherein the derivative is represented by the following formula (VII):
• ##STR324## wherein W is CH, wherein j is O and K is 1, or j is l and k is 0,
• wherein R.sub.1 and R.sub.2 are each independently C.sub.1 -C.sub.5 -alkyl,
• wherein R.sub.5 is H or methyl, and
• wherein A is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, naphthyl, furyl, thienyl, pyridyl or pyrimidinyl.

A quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (VIII):

• ##STR325## wherein W is CH, wherein R.sub.1 and R.sub.2 are each independently C.sub.1 -C.sub.5 -alkyl, each R.sub.5 is independently H or methyl,
• wherein A is C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.4 -alkenyl, cyclopentyl, cyclohexyl, cycloheptyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, acetyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl or morpholino,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is methyl.

A quinoline derivative, or a pharmaceutically acceptable salt thereof,

• wherein the derivative is represented by the following formula (IX):
• ##STR326## wherein W is CH, wherein R.sub.1 and R.sub.2 are each independently C.sub.1 -C.sub.5 -alkyl,
• wherein each R.sub.5 is independently H or methyl, and
• wherein A is C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.4 -alkenyl, cyclopentyl, cyclohexyl, cycloheptyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, acetyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl or morpholino.

A quinoline derivative, or a pharmaceutically acceptable salt thereof,

• wherein the derivative is represented by the following formula (X):
• ##STR327## wherein R.sub.1 and R.sub.2 are each independently C.sub.1 -C.sub.5 -alkyl,
• wherein R.sub.5 is each independently hydrogen or methyl, and
• wherein A is C.sub.1 -C.sub.5 -alkyl, cyclopentyl, cyclohexyl, cycloheptyl, allyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl or benzoyl.

A method for treating a tumor comprising administering to a patient suffering from a tumor an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR329## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR330## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating psoriasis comprising administering to a patient suffering from psoriasis an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR331## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR332## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating atherosclerosis comprising administering to a patient suffering from atherosclerosis an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR333## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR334## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating restenosis after percutaneous coronary angioplasty or bypass surgery comprising administering to a patient suffering from restenosis after percutaneous coronary angioplasty or bypass surgery an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR335## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR336## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating glomerulonephritis comprising administering to a patient suffering from glomerulonephritis an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR337## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR338## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating organofibrosis comprising administering to a patient suffering from organofibrosis an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR339## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR340## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating leukemia comprising administering to a patient suffering from leukemia an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR341## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR342## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).

A method for treating articular rheumatism comprising administering to a patient suffering from articular rheumatism an effective amount of a quinoline derivative, or a pharmaceutically acceptable salt thereof, wherein the derivative is represented by the following formula (I):

• ##STR343## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.5 -alkyl or together form C.sub.1 -C.sub.3 -alkylene,
• wherein W is CH,
• wherein X is O, S or CH.sub.2,
• wherein Q is a group represented by the following formula (II), (III), (IV) or (V):
• ##STR344## wherein m is 1, 2 or 3, wherein each R.sub.3 is independently CN, OH, halogen, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.2 -C.sub.4 -acyl,
• wherein each R.sub.3 ' is independently OH, C.sub.1 -C.sub.5 -alkyl or C.sub.1 -C.sub.4 -alkoxy,
• wherein Y and Z are each independently N or CH,
• wherein R.sub.4 is H, C.sub.1 -C.sub.5 -alkyl or C.sub.2 -C.sub.4 -acyl,
• wherein j and k are each independently 0 or 1,
• wherein each R.sub.5 is independently H or C.sub.1 -C.sub.4 -alkyl,
• wherein A is C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkenyl, cyclic (C.sub.3 -C.sub.10)-alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, naphthyl, furyl, thienyl, benzoyl, substituted benzoyl, C.sub.2 -C.sub.4 -acyl, or a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl group,
• wherein the heteroaryl group has 1 or 2 nitrogen atoms,
• wherein B is O, S, NH, NCN, NR.sub.6 or NOR.sub.6, and
• wherein R.sub.6 is C.sub.1 -C.sub.5 -alkyl,
• with the proviso that if X is CH.sub.2, then Q is not a group represented by the formula (II), (III) or (IV).