# US 9,434,734 B2 · Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors

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- Number: US 9,434,734 B2
- Document ID: US9434734B2
- Status: Granted
- Kind: B2
- Application number: 14/403,070
- Filed: 2013-05-21
- Published: 2015-04-16
- Granted: 2016-09-06
- Earliest claimed: 2012-05-21
- Assignees: Domain Therapeutics
- Applicants: Domain Therapeutics
- Inventors: Stanislas Mayer; Stephan Schann
- Web page: https://patentgrep.com/patent/US9434734B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 35/00: Antineoplastic agents
- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- G01N 33/9406: {Neurotransmitters}
- G01N 2333/726: G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- G01N 2500/10: involving cells
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.

## Claims

### Claim 1

A compound of formula (I):
wherein:
A is N or C(H);
B is aryl or heteroaryl;
each R1 is independently selected from R5, halogen, —CF3, —CN, —OR5, —OCF3, —NR5R6,—COOR5, tetrazolyl, —SO3H, —B(OH)2, —CONR5R6, —COR5, —SR5, —SOR5, —SO2R5, —SO2NR5R6, —NR5COR6, —NR5SO2R6 or —OCOR5;
n1 is 1,2 or 3;
each R2 is independently selected from R5, halogen, —CF3, —CN, —OR5, —OCF3, —NR5R6, —COOR5, —CONR5R6, —COR5, —SR5, —SOR5, —SO2R5, SO2NR5R6, —NR5COR6, —NR5SO2R6, or —OCOR5;
n2 is 1, 2 or 3;
R3 is a -L-R7 group, wherein:
L is a bond or C1-C4 alkylene, wherein one or more —CH2— units comprised in said alkylene are each optionally replaced by a group independently selected from —O—,—NR5—, —CO—, —S—, —SO—, or —SO2—; and
R7 is selected from hydrogen, halogen, —CF3, —CN, an optionally substituted C1-C4 alkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted aryl, or an optionally substituted heteroaryl, wherein said C1-C4 alkyl, said cycloalkyl, said heterocycloalkyl, said aryl or said heteroaryl is optionally substituted with one or more groups independently selected from R5, halogen, —CF3, —CN, —NR5R6, —CONR5R6, —COR5, —OR5, —SR5, —SOR5, —SO2R5, —SO2N R5R6, —NR5COR6, —NR5SO2R6, —OCOR5, —COOR5, tetrazolyl, —SO3H, or —B(OH)2;
R4 is selected from an optionally substituted C1-C4 alkyl, an optionally substituted cycloalkyl, or an optionally substituted heterocycloalkyl, wherein said C1-C4 alkyl is optionally substituted with one or more groups independently selected from cycloalkyl, halogen, —CF3, —CN, —OH or —O(C1-C4 alkyl), and further wherein said cycloalkyl or said heterocycloalkyl is optionally substituted with one or more groups independently selected from C1-C4 alkyl, cycloalkyl, halogen, —CF3, —CN, —OH or —O(C1-C4 alkyl); and
each R5 and each R6 is independently selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted cycloalkyl, or an optionally substituted heterocycloalkyl, wherein said C1-C4 alkyl is optionally substituted with one or more groups independently selected from halogen, —CF3, —CN, —OH, —O(C1-C4 alkyl), —NH2, —NH(C1-C4 alkyl) or —N(C1-C4 alkyl)(C1-C4 alkyl), and further wherein said cycloalkyl and said heterocycloalkyl are each optionally substituted with one or more groups independently selected from C1-C4 alkyl, halogen, —CF3, —CN, —OH, —O(C1-C4 alkyl), —NH2, —NH(C1-C4 alkyl) or —N(C1-C4 alkyl)(C1-C4 alkyl);
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein A is N.

### Claim 3 (depends on 1)

The compound of claim 1, wherein A is C(H).

### Claim 4 (depends on 1)

The compound of claim 1, wherein B is phenyl or B is a heteroaryl having 5 or 6 ring members and comprising one or more ring heteroatoms independently selected from O, S, or N,
and further wherein each R1 is independently selected from C1-C4 alkyl, halogen, —CF3, —CN, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)(C1-C4 alkyl), —COOH, —COO(C1-C4 alkyl), tetrazol-5-yl, —SO3H, —CO(C1-C4 alkyl), —SO2(C1-C4 alkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), or —SO2N(C1-C4 alkyl)(C1-C4 alkyl).

### Claim 5 (depends on 1)

The compound of claim 1, wherein the moiety —(B)—(R1)n1 is selected from phenyl, pyridinyl, pyrazolyl, oxazolyl, tetrazolyl, pyrimidinyl, pyridazinyl, or pyrazinyl, wherein said phenyl, said pyridinyl, said pyrazolyl, said oxazolyl, said tetrazolyl, said pyrimidinyl, said pyridazinyl or said pyrazinyl is substituted with one, two or three groups selected independently from methyl, ethyl, halogen, —CF3, —CN, —NH2, —NH(CH3), —N(CH3)2, —COOH, tetrazol-5-yl, —COCH3, —SO2NH2, —SO2NH(CH3), or —SO2N(CH3)2.

### Claim 6 (depends on 1)

The compound of claim 1, wherein n2 is 1 and R2 is hydrogen.

### Claim 7 (depends on 1)

The compound of claim 1, wherein L is a bond or C1-C4 alkylene, wherein one —CH2— unit comprised in said alkylene is optionally replaced by —O—,
and further wherein R7 is selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted aryl, or an optionally substituted heteroaryl, wherein said C1-C4 alkyl is optionally substituted with one or more groups independently selected from halogen, —CF3, —CN, —OH, —O(C1-C4 alkyl), —NH2, —NH(C1-C4 alkyl) or —N(C1-C4 alkyl)(C1-C4 alkyl), and further wherein said cycloalkyl, said heterocycloalkyl, said aryl or said heteroaryl is optionally substituted with one or more groups independently selected from C1-C4 alkyl, halogen, —CF3, —CN, —OH, —O(C1-C4 alkyl), —NH2, —NH(C1-C4 alkyl) or —N(C1-C4 alkyl)(C1-C4 alkyl).

### Claim 8 (depends on 1)

The compound of claim 1, wherein R4 is selected from an optionally substituted C1-C4 alkyl, a cycloalkyl, or a heterocycloalkyl, wherein said C1-C4 alkyl is optionally substituted with one or more groups independently selected from cycloalkyl, halogen, —CF3, —CN, —OH or —O(C1-C4 alkyl).

### Claim 9 (depends on 1)

The compound of claim 1, wherein each R5 and each R6 is independently selected from hydrogen, an optionally substituted C1-C4 alkyl or an optionally substituted heterocycloalkyl, wherein said C1-C4 alkyl is optionally substituted with one or more groups independently selected from halogen or —CF3, and further wherein said heterocycloalkyl is optionally substituted with one or more groups independently selected from C1-C4 alkyl, halogen, or —CF3.

### Claim 10 (depends on 1)

The compound of claim 1, wherein said compound is selected from:
8-(6-Amino-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(4-Amino-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(6-morpholin-4-yl-pyridin-3-yl)-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-phenyl-8-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-phenyl-8-(1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(4-Methoxy-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-Imidazo[1,2-a]pyridin-6-yl-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one; 8-(3-Methoxymethyl-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one; 4-(4-Methyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzenesulfonamide;
8-(3-Methoxy-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(4-Fluoro-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(4-Chloro-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(3-Acetyl-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(3,5-Dimethyl-1H-pyrazol-4-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-phenyl-8-(1H-pyrazol-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(3-methyl-1H-pyrazol-4-yl)-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-phenyl-8-(3-trifluoromethyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-oxazol-2-yl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-oxazol-5-yl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-phenyl-8-(2H-tetrazol-5-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(3-Bromo-phenyl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-4-methyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-2-methyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-5-methyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-2-ethyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-2,4-dimethyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridazin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(5-Amino-pyrazin-2-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2-Amino-pyrimidin-5-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(5-Amino-3-methyl-pyrazin-2-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-2-trifluoromethyl-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
3-(4-Methyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzoic acid;
3-(4-Methyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzonitrile;
4-Methyl-2-phenyl-8-[3-(2H-tetrazol-5-yl)-phenyl]-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
N,N-Dimethyl-3-(4-methyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzenesulfonamide;
N,N-Dimethyl-3-(4-Ethyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzenesulfonamide;
N,N-Dimethyl-3-(4-propyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-benzenesulfonamide;
3-(4-Isobutyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-N,N-dimethyl-benzenesulfonamide;
3-(4-Cyclopropylmethyl-5-oxo-2-phenyl-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl)-N,N-dimethyl-benzenesulfonamide;
8-(6-Amino-pyridin-3-yl)-4-ethyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-phenyl-4-propyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-phenyl-4-(2,2,2-trifluoro-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-(2,2-difluoro-ethyl)-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-isopropyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-cyclobutyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-ethyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-propyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-isopropyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-tert-butyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(2-methoxy-ethyl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-2-(2-methoxy-ethyl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(2-methoxy-ethyl)-4-methyl(D 3)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-2-(2-methoxy-ethyl)-4-methyl(D 3)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-ethyl-2-(2-methoxy-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-ethyl-2-(2-methoxy-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(2-methoxy-ethyl)-4-propyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-2-(2-methoxy-ethyl)-4-propyl-4H-pyrazolo[1,5-a]quinazolin 5-one;
8-(6-Amino-pyridin-3-yl)-2-methoxymethyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-2-methoxymethyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclopropyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclobutyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclopentyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclopentyl-8-(2,6-dimethyl-pyridin-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclopentyl-4-methyl(D 3)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclopentyl-8-(2,6-dimethyl-pyridin-4-yl)-4-methyl(D 3)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclopentyl-4-ethyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclopentyl-8-(2,6-dimethyl-pyridin-4-yl)-4-ethyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclopentyl-4-propyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclopentyl-8-(2,6-dimethyl-pyridin-4-yl)-4-propyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclopentyl-8-(2,6-dimethyl-pyridin-4-yl)-4-(2,2,2-trifluoro-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cyclohexyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cyclohexyl-4-methyl-8-(3-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-cycloheptyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cycloheptyl-8-(2,6-dimethyl-pyridin-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-Cycloheptyl-8-(2,6-dimethyl-pyridin-4-yl)-4-ethyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-benzyl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(4-fluoro-phenyl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(4-Fluoro-phenyl)-4-methyl-8-(3-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-furan-2-yl-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-(tetrahydro-thiopyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one; 8-(6-Amino-pyridin-3-yl)-2-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-pyridin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(1H-pyrazol-4-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
3-[4-Methyl-5-oxo-2-(tetrahydro-pyran-4-yl)-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl]-benzonitrile;
4-Methyl-8-pyridin-3-yl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-pyridin-4-yl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-oxazol-2-yl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(5-methyl-1H-pyrazol-4-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(2-methyl-pyridin-4-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(2-methyl-pyridin-3-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(6-methyl-pyridin-3-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(tetrahydro-pyran-4-yl)-8-[3-(2H-tetrazol-5-yl)-phenyl]-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridazin-3-yl)-4-methyl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-3-yl)-4-methyl-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
3-[4-Methyl-5-oxo-2-(tetrahydro-pyran-4-yl)-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl]-benzenesulfonamide;
N-(2-Hydroxy-1,1-dimethyl-ethyl)-3-[4-methyl-5-oxo-2-(tetrahydro-pyran-4-yl)-4,5-dihydro-pyrazolo[1,5-a]quinazolin-8-yl]benzenesulfonamide;
4-(2,2-Difluoro-ethyl)-8-(2,6-dimethyl-pyridin-4-yl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-(2,2-difluoro-ethyl)-2-(tetrahydro-pyran-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(tetrahydro-pyran-4-yl)-4-(2,2,2-trifluoro-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-2-(tetrahydro-pyran-4-yl)-4-(2,2,2-trifluoro-ethyl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(tetrahydro-furan-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(tetrahydro-furan-2-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(tetrahydro-pyran-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(tetrahydro-pyran-2-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-phenyl-4H-pyrrolo[1,2-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-phenyl-4H-pyrrolo[1,2-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(2,6-dimethyl-pyridin-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(2-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2,8-Bis-(2,6-dimethyl-pyridin-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-pyridin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(6-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(5-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one,
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(4-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-8-(2-ethyl-pyridin-3-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(3-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(1-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(2H-pyrazol-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-8-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(4-Methoxy-phenyl)-4-methyl-2-(1-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-8-pyridin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-8-(2-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-(1-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-8-pyridin-4-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(1-methyl-1H-pyrazol-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-2-(1-ethyl-1H-pyrazol-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2-methyl-pyridin-4-yl)-4-methyl-8-(2-methyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-2-(2-methyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(2-methyl-pyridin-3-yl)-2-pyridin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(2-methyl-pyridin-3-yl)-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Amino-pyridin-3-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2-Ethyl-pyridin-3-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(2-methyl-pyridin-4-yl)-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2,8-bis-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2-Fluoro-pyridin-4-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(6-Fluoro-pyridin-3-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-2-(2-trifluoromethyl-pyridin-4-yl)-8-(2-trifluoromethyl-pyridin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(2,6-Dimethyl-pyridin-3-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
4-Methyl-8-(4-methyl-pyrimidin-5-yl)-2-(2-trifluoromethyl-pyridia]quinazolin-5-one;
8-(3,5-Dimethyl-1H-pyrazol-4-yl)-4-methyl-2-(2-trifluoromethyl-pyridin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;
8-(3,5-Dimethyl-1H-pyrazol-4-yl)-2-(2,6-dimethyl-pyridin-4-yl)-4-methyl-4H-pyrazolo[1,5-a]quinazolin-5-one;
2-(2,6-Dimethyl-pyridin-4-yl)-4-methyl-8-(3-trifluoromethyl-1H-pyrazol-4-yl)-4H pyrazolo[1,5-a]quinazolin-5-one;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

### Claim 12 (depends on 1)

The compound or a pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient for use in treating a condition associated with altered glutamatergic signalling and/or functions, or a condition which can be affected by alteration of glutamate level or signalling.

### Claim 13 (depends on 12)

The compound or the pharmaceutical composition of claim 12, wherein the condition to be treated is selected from: epilepsy; dementias; parkinsonism and movement disorders; motor neuron disease or amyotrophic lateral sclerosis; neurodegenerative and/or hereditary disorders of the nervous system; disorders of the peripheral nervous system; multiple sclerosis and other demyelinating diseases of the nervous system; infantile cerebral palsy; paralytic syndromes including hemiplegia and hemiparesis; cerebrovascular disorders; migraine; headache; myoneural disorders; disorders of the eye and visual pathways; intracranial trauma/injury and their sequels; trauma/injury to nerves and spinal cord and their sequels; poisoning and toxic effects of nonmedicinal substances; accidental poisoning by drugs, medicinal substances and biologicals acting on the central, peripheral and autonomic system; neurological and psychiatric adverse effects of drugs, medicinal and biological substances; disturbance of sphincter control and sexual function; mental disorders; delirium and cognitive disorders; substance related disorders; schizophrenia and psychotic disorders; mood disorders; anxiety disorders; eating disorders; sleep disorders; medication-induced movement disorders; endocrine and metabolic diseases; acute and chronic pain; nausea and vomiting; irritable bowel syndrome; or cancers.

### Claim 14 (depends on 13)

The compound or the pharmaceutical composition of claim 13, wherein the condition to be treated is selected from: dementias; parkinsonism and movement disorders; acute or chronic pain; anxiety disorders; schizophrenia; mood disorders; endocrine or metabolic diseases; or cancers;
and further wherein said dementias are selected from: dementias of the Alzheimer's type (DAT); Alzheimer's disease; Pick's disease; vascular dementias; Lewy-body disease; dementias due to metabolic, toxic and deficiency diseases, including alcoholism, hypothyroidism, and vitamin B12 deficiency; AIDS-dementia complex; Creutzfeld-Jacob disease; or atypical subacute spongiform encephalopathy;
wherein said parkinsonism and movement disorders are selected from: Parkinson's disease; multiple system atrophy; progressive supranuclear palsy; corticobasal degeneration; hepatolenticular degeneration; chorea, including Huntington's disease and hemiballismus; athetosis; dystonias, including spasmodic torticollis, occupational movement disorder, and Gilles de la Tourette syndrome; tardive or drug induced dyskinesias; tremor; or myoclonus;
wherein said anxiety disorders are selected from: panic disorders, phobias, obsessive-compulsive disorders, stress disorders, or generalized anxiety disorders;
wherein said mood disorders are selected from depressive disorders or bipolar disorders;
wherein said endocrine or metabolic diseases are selected from: diabetes; disorders of the endocrine glands; or hypoglycaemia; and
wherein said cancers are selected from: gliomas; colorectal cancer; melanoma; or prostate cancer.

### Claim 15 (depends on 1)

A method for identifying an agent that binds to metabotropic glutamate receptor 2 (mGluR2) or to metabotropic glutamate receptor 3 (mGluR3), comprising the following steps:
(a) contacting mGluR2 or mGluR3 with the compound of claim 1, wherein said compound is radio-labeled or fluorescence-labeled, under conditions that permit binding of the compound to mGluR2 or mGluR3, thereby generating bound, labeled compound;
(b) detecting a signal that corresponds to the amount of bound, labeled compound in the absence of test agent;
(c) contacting the bound, labeled compound with a test agent;
(d) detecting a signal that corresponds to the amount of bound labeled compound in the presence of test agent; and
(e) comparing the signal detected in step (d) to the signal detected in step (b) to determine whether the test agent binds to mGluR2 or mGluR3.