US 6,608,085 B1 · 4-quinolinemethanol derivatives as purine receptor antagonists (II)

Abstract

Use of a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt or prodrug thereof, in the manufacture of a medicament for the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A2a receptors, may be beneficial, such as a movement disorder, for example, Parkinson's Disease or progressive supemuclear palsy, Huntingtons disease, multiple system atrophy, corticobasal degeneration, Wilsons disease, Hallerrorder-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity, Alzheimer's disease or other disorders of the basal ganglia which result in dyskinesias.

A method of treating a disorder in which the blocking of adenosine A2A receptor is beneficial, comprising administering to a subject in need of such treatment an effective dose of a compound of formula I:

wherein:
R1 is hydrogen or alkyl;
R2 is selected from the group consisting of hydrogen, alkyl, aryl and 4, 5, 6, 7 or 8 membered saturated or partially unsaturated heterocyclic rings containing one or more heteroatoms selected from O, S and N;
R3 and R4 are independently selected from the group consisting of hydrogen, alkyl, aryl, COR13, CO2R13, CONR13R14, CONR13NR14R15, SO2R13, SO2NR13R14, SO2NR13NR14R15 and 4, 5, 6, 7 or 8 membered saturated or partially unsaturated heterocyclic rings containing one or more heteroatoms selected from O, S and N, or together may form a 3, 4, 5, 6, 7 or 8 membered saturated, partially unsaturated or aromatic heterocyclic ring optionally containing one or more additional heteroatoms selected from the group consisting of O, S and N;
or R1 and R4 together may form a 5, 6 or 7 membered saturated or partially unsaturated heterocyclic ring optionally containing an additional heteroatom selected from the group consisting of O, S and N;
or R2 and R3 together may form a 4, 5, 6 or 7 membered saturated or partially unsaturated heterocyclic ring optionally containing one or more additional heteroatoms selected from the group consisting of O, S and N;
R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aryl and 4, 5, 6, 7 or 8 membered saturated or partially unsaturated heterocyclic rings containing one or more heteroatoms selected from the group consisting of O, S and N, or together may form a 3, 4, 5, 6 or 7 membered saturated or partially unsaturated carbocyclic ring or a 4, 5, 6, 7 or 8 membered saturated or partially unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of O, S and N;
or R3 and R5 together may form a 4, 5, 6 or 7 membered unbridged, saturated or partially unsaturated heterocyclic ring optionally containing one or more additional heteroatoms selected from the group consisting of O, S and N;
wherein said carbocyclic or said heterocyclic ring when partially unsaturated or aromatic may be fused to an aryl ring;
and wherein said disorder is selected from the group consisting of movement disorders and depression;
with the proviso that where R3 and R5 together form a ring, then R3 and R4 do not also form a ring;
R7, R8, R9, R10, R11 and R12 are independently selected from the group consisting of hydrogen, alkyl, aryl, 4, 5, 6, 7 or 8 membered saturated or partially unsaturated heterocyclic rings containing one or more heteroatoms selected from the group consisting of O, S and N, hydroxy, halogen, nitro, cyano, alkoxy, aryloxy, COR13, OCOR13, CO2R13, SR13, SOR13, SO2R13, SO2NR13R14, CONR13R14, CONR13NR14R15, OCONR13R14, NR13R14, NR13COR14, NR15 CONR13R14, NR13CO2R14, NR13SO2R14, CR13NOR14, NR13CONR14NR15R16, NR13NR14CO2R15, NR13 NR14CONR15R16, NR13NR14COR15, NR13NR14SO2R15, SO2NR13NR14R15, NR13 SO2NR14NR15R16 and NR13SO2NR14R15, wherein R13, R14, R15 and R16 are independently selected from the group consisting of hydrogen, alkyl and aryl,
or a pharmaceutically acceptable salt thereof.

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4-quinolinemethanol derivatives as purine receptor antagonists (II)

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4-quinolinemethanol derivatives as purine receptor antagonists (II)

Life of this patent

Abstract

Claims33