Pyrazolopyrimidines for treating CNS disorders

A method for treating or preventing a condition or disease associated with abnormal glutamate neurotransmission or a method for modulating mGluR5 receptors to achieve therapeutic benefit, in a subject in need thereof comprising administering a therapeutically effective amount of a compound selected from those of formula (I):

• wherein,
• Y1 represents N or C—,
• Y2 represents N or C—,
• Y3 represents N or C—, and
• Y4 represents N or C—,
• wherein at least two of the groups Y1 to Y4 represent a carbon atom;
• R1 represents chloro or bromo;
• R2 and R3 each independently represent hydrogen, C1-6alkyl, C3-7cycloalkyl or trifluoromethyl;
• or
• R2 and R3 both together with the carbon atom of the ring represent a carbonyl group;
• R4 and R5 each independently represent hydrogen, C1-6alkyl, C3-7cycloalkyl or trifluoromethyl;
• or
• R4 and R5 both together with the carbon atom of the ring represent a carbonyl group;
• R6 and R7 independently represent hydrogen, C1-6-alkyl, C3-7cycloalkyl or trifluoromethyl;
• or
• R6 and R7 both together with the carbon atom of the ring represent a carbonyl group;
• R2 or R3 together with R6 and R7 may also form a bivalent radical selected from the group CH2—CH2 and CH2—O;
• R10 and R11 independently represent hydrogen, halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, aryl, C1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C3-7-cycloalkyloxy, C2-6alkenyloxy, C2-6alkynyloxy, heteroaryl, heterocyclyl, aryloxy, heteroaryloxy, heterocyclyloxy, C1-6alkylamino, di-C1-6alkylamino, C3-7-cycloalkylamino, di-C3-7-cycloalkylamino, C1-6alkyl-C3-7-cycloalkylamino, C2-6alkenylamino, C2-6alkynylamino, di-C2-6alkenylamino, di-C2-6alkynylamino, C1-6alkyl-C2-6-alkenylamino, C1-6alkyl-C2-6-alkynylamino, C2-6alkenyl-C3-7-cycloalkylamino, C2-6alkynyl-C3-7-cycloalkylamino, C2-6alkenyl-C2-6-alkynylamino, arylamino, diarylamino, aryl-C1-6alkylamino, aryl-C2-6alkenylamino, aryl-C2-6alkynylamino, aryl-C3-7-cycloalkylamino, heteroarylamino, diheteroarylamino, heteroaryl-C1-6alkylamino, heteroaryl-C2-6alkenylamino, heteroaryl-C2-6alkynylamino, heteroaryl-C3-7-cycloalkylamino, heteroarylarylamino, heterocyclylamino, diheterocyclylamino, heterocyclyl-C1-6alkylamino, heterocyclyl-C2-6alkenylamino, heterocyclyl-C2-6alkynylamino, heterocyclyl-C3-7-cycloalkylamino, heterocyclylarylamino, heterocyclylhetero-arylamino, acyl, acyloxy, acylamino, C1-6alkoxycarbonyl, C3-7-cycloalkoxy-carbonyl, C2-6alkenyloxycarbonyl, C2-6alkynyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocyclyloxycarbonyl, aminocarbonyl, C1-6alkylamino-carbonyl, di-C1-6alkylaminocarbonyl, C3-7-cycloalkylaminocarbonyl, di-C3-7-cycloalkylaminocarbonyl, C1-6alkyl-C3-7-cycloalkylaminocarbonyl, C2-6alkenyl-aminocarbonyl, C2-6alkynylaminocarbonyl, di-C2-6alkenylaminocarbonyl, di-C2-6alkynylaminocarbonyl, C1-6alkyl-C2-6-alkenyl aminocarbonyl, C1-6alkyl-C2-6-alkynyl-aminocarbonyl, C2-6alkenyl-C3-7-cycloalkylaminocarbonyl, C2-6alkynyl-C3-7-cycloalkylaminocarbonyl, C2-6alkenyl-C2-6-alkynylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aryl-C1-6alkylaminocarbonyl, aryl-C2-6alkenylaminocarbonyl, aryl-C2-6alkynylaminocarbonyl, aryl-C3-7-cycloalkylaminocarbonyl heteroarylaminocarbonyl, diheteroarylaminocarbonyl, heteroaryl-C1-6alkylaminocarbonyl, heteroaryl-C2-6alkenylaminocarbonyl, heteroaryl-C2-6alkynylaminocarbonyl, heteroaryl-C3-7-cycloalkylaminocarbonyl, heteroarylarylaminocarbonyl, heterocyclylaminocarbonyl, diheterocyclylamino-carbonyl, heterocyclyl-C1-6alkylaminocarbonyl, heterocyclyl-C2-6alkenylamino-carbonyl, heterocyclyl-C2-6alkynylaminocarbonyl, heterocyclyl-C3-7-cycloalkyl-aminocarbonyl, heterocyclylarylaminocarbonyl, heterocyclylheteroarylamino-carbonyl, C1-6alkylsulfinyl, C3-7-cycloalkylsulfinyl, C2-6alkenylsulfinyl, C2-6alkynylsulfinyl, arylsulfinyl, heteroarylsulfinyl, heterocyclylsulfinyl, C1-6alkylsulfonyl, C3-7-cycloalkylsulfonyl, C2-6alkenylsulfonyl, C2-6alkynylsulfonyl, arylsulfonyl, heteroarylsulfonyl, heterocyclylsulfonyl, C1-6alkylsulfonylamino, or arylsulfonylamino;
• or R10 and R11 together with the two carbon atoms carrying them represent a heteroaryl having 5 or 6 ring members or a heterocyclyl group having 5 or 6 ring members, which can be substituted by one of the following groups:
• halogen, hydroxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, C1-6alkyl and C1-6alkoxy;
• and optical isomers, pharmaceutically acceptable salts, hydrates, solvates, and polymorphs thereof.