THERAPEUTIC AGENT FOR MOTOR DISORDERS
Provided are an agent for the treatment and/or prophylaxis of a movement disorder, the agent for the treatment and/or prophylaxis wherein the movement disorder is extrapyramidal syndrome, the agent for the treatment and/or prophylaxis wherein the movement disorder is bradykinesia, gait disturbance, dystonia, dyskinesia or tardive dyskinesia, the agent for the treatment and/or prophylaxis wherein the movement disorder is a side effect of L-DOPA and/or dopamine agonist therapy, and the like, each containing a thiazole derivative represented by the formula (I) wherein R 1 represents aryl and the like, and R 2 represents pyridyl or the like, or a pharmaceutically acceptable salt thereof as an active ingredient.
1 - 11 . (canceled)
12 . A pharmaceutical composition comprising:
(a) a thiazole derivative represented by formula (I)
wherein R 1 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2 represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
(b) L-DOPA and/or a dopamine agonist.
13 . The pharmaceutical composition according to claim 12 , wherein R 1 is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof.
14 . The pharmaceutical composition according to claim 13 , wherein R 2 is pyridyl, or a pharmaceutically acceptable salt thereof.
15 . The pharmaceutical composition according to claim 13 , wherein R 2 is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof.
16 . The pharmaceutical composition according to claim 12 , wherein the thiazole derivative is represented by formulas (IA)-(IAA):
or a pharmaceutically acceptable salt thereof.
17 - 22 . (canceled)
23 . A kit, comprising:
(a) a first component comprising a thiazole derivative represented by formula (I)
wherein R 1 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2 represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
(b) a second component comprising L-DOPA and/or a dopamine agonist.
24 . The kit according to claim 23 , wherein R 1 is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof.
25 . The kit according to claim 24 , wherein R 2 is pyridyl, or a pharmaceutically acceptable salt thereof.
26 . The kit according to claim 24 , wherein R 2 is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof.
27 . The kit according to claim 23 , wherein the thiazole derivative is represented by one of formulas (IA)-(IAA):
or a pharmaceutically acceptable salt thereof.
28 . A method of treating and/or preventing progression of a movement disorder, comprising the steps of:
administering to a patient an effective amount of a thiazole derivative represented by formula (I)
wherein R 1 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2 represents pyridyl or tetrahydropyranyl,
or a pharmaceutically acceptable salt thereof.
29 . The method according to claim 28 , wherein R 1 is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof.
30 . The method according to claim 29 , wherein R 2 is pyridyl, or a pharmaceutically acceptable salt thereof.
31 . The method according to claim 29 , wherein R 2 is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof.
32 . The method according to claim 28 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA):
or a pharmaceutically acceptable salt thereof.
33 . The method according to claim 28 , wherein the movement disorder is extrapyramidal syndrome.
34 . The method according to claim 28 , wherein the movement disorder is bradykinesia, gait disturbance, dystonia, dyskinesia or tardive dyskinesia.
35 . The method according to claim 28 , wherein the movement disorder is a side effect of L-DOPA and/or dopamine agonist therapy.
36 . The method according to claim 35 , wherein the side effect is a motor complication.
37 . The method according to claim 36 , wherein the motor complication is wearing-off phenomenon.
38 . The method according to claim 36 , wherein the motor complication is on-off fluctuation.
39 . A method of treating and/or preventing progression of Parkinson's disease, comprising the steps of:
administering to a patient simultaneously or separately at an interval (a) an effective amount of a thiazole derivative represented by formula (I)
wherein R 1 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2 represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
(b) an effective amount of L-DOPA and/or a dopamine agonist.
40 . The method according to claim 39 , wherein R 1 is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof.
41 . The method according to claim 40 , wherein R 2 is pyridyl, or a pharmaceutically acceptable salt thereof.
42 . The method according to claim 40 , wherein R 2 is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof.
43 . The method according to claim 39 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA):
or a pharmaceutically acceptable salt thereof.
44 - 54 . (canceled)
55 . A compound represented by any one of the following formulas (IE)-(IAA), or a pharmaceutically acceptable salt thereof:
56 . A combination of:
(a) a thiazole derivative represented by formula (I)
wherein R 1 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2 represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
(b) L-DOPA and/or a dopamine agonist, for use in the treatment and/or prophylaxis of Parkinson's disease.
57 . The combination according to claim 56 , wherein (a) and (b) are administered simultaneously.
58 . The combination according to claim 56 , wherein R 1 is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof.
59 . The combination according to claim 58 , wherein R 2 is pyridyl, or a pharmaceutically acceptable salt thereof.
60 . The combination according to claim 58 , wherein R 2 is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof.
61 . The combination according to claim 56 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA):
or a pharmaceutically acceptable salt thereof.
62 - 73 . (canceled)
74 . The combination according to claim 56 , wherein (a) and (b) are administered separately at an interval.
75 - 78 . (canceled)