| Rank |
Title |
Journal |
Year |
PubWeight™‹?› |
|
1
|
Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.
|
J Med Chem
|
2012
|
2.10
|
|
2
|
Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.
|
Mol Pharmacol
|
2010
|
1.93
|
|
3
|
An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission.
|
Nat Chem Biol
|
2007
|
1.83
|
|
4
|
Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.
|
Science
|
2014
|
1.81
|
|
5
|
A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning.
|
Mol Pharmacol
|
2009
|
1.76
|
|
6
|
Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity.
|
Mol Pharmacol
|
2008
|
1.68
|
|
7
|
Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).
|
J Med Chem
|
2009
|
1.59
|
|
8
|
Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins.
|
J Med Chem
|
2009
|
1.57
|
|
9
|
Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system.
|
ACS Chem Neurosci
|
2010
|
1.52
|
|
10
|
mGluR4-positive allosteric modulation as potential treatment for Parkinson's disease.
|
Future Med Chem
|
2009
|
1.47
|
|
11
|
Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function.
|
Mol Pharmacol
|
2011
|
1.46
|
|
12
|
Glutamate receptors as therapeutic targets for Parkinson's disease.
|
CNS Neurol Disord Drug Targets
|
2009
|
1.30
|
|
13
|
Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model.
|
J Med Chem
|
2011
|
1.29
|
|
14
|
Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe.
|
Bioorg Med Chem Lett
|
2010
|
1.27
|
|
15
|
Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology.
|
ACS Chem Neurosci
|
2010
|
1.24
|
|
16
|
Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease.
|
Curr Top Med Chem
|
2009
|
1.24
|
|
17
|
Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity.
|
Biol Psychiatry
|
2012
|
1.22
|
|
18
|
Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.
|
Bioorg Med Chem Lett
|
2010
|
1.21
|
|
19
|
Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380).
|
J Med Chem
|
2014
|
1.17
|
|
20
|
A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors.
|
J Pharmacol Exp Ther
|
2007
|
1.16
|
|
21
|
Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.
|
Bioorg Med Chem Lett
|
2008
|
1.16
|
|
22
|
Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships.
|
Mol Pharmacol
|
2012
|
1.15
|
|
23
|
The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.
|
J Pharmacol Exp Ther
|
2011
|
1.14
|
|
24
|
Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models.
|
J Neurosci
|
2012
|
1.13
|
|
25
|
Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor.
|
Bioorg Med Chem Lett
|
2012
|
1.10
|
|
26
|
Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics.
|
ACS Chem Biol
|
2014
|
1.09
|
|
27
|
Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated.
|
Neuropharmacology
|
2007
|
1.09
|
|
28
|
Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS).
|
Bioorg Med Chem Lett
|
2010
|
1.09
|
|
29
|
Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4.
|
ACS Chem Neurosci
|
2010
|
1.07
|
|
30
|
Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents.
|
ACS Chem Neurosci
|
2014
|
1.06
|
|
31
|
Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe.
|
ChemMedChem
|
2014
|
1.05
|
|
32
|
ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice.
|
ACS Chem Neurosci
|
2013
|
1.04
|
|
33
|
Biotransformation of a novel positive allosteric modulator of metabotropic glutamate receptor subtype 5 contributes to seizure-like adverse events in rats involving a receptor agonism-dependent mechanism.
|
Drug Metab Dispos
|
2013
|
1.04
|
|
34
|
Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold.
|
Bioorg Med Chem Lett
|
2011
|
1.04
|
|
35
|
Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM.
|
Bioorg Med Chem Lett
|
2012
|
1.03
|
|
36
|
Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats.
|
J Med Chem
|
2011
|
1.01
|
|
37
|
Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists.
|
Bioorg Med Chem Lett
|
2008
|
1.01
|
|
38
|
Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169.
|
ACS Chem Neurosci
|
2012
|
1.01
|
|
39
|
The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5.
|
Drug Metab Dispos
|
2012
|
0.99
|
|
40
|
Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.
|
Chem Rev
|
2016
|
0.97
|
|
41
|
Dihydrothiazolopyridone derivatives as a novel family of positive allosteric modulators of the metabotropic glutamate 5 (mGlu5) receptor.
|
J Med Chem
|
2013
|
0.97
|
|
42
|
Discovery of ML326: The first sub-micromolar, selective M5 PAM.
|
Bioorg Med Chem Lett
|
2013
|
0.97
|
|
43
|
Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS.
|
J Neurosci
|
2014
|
0.96
|
|
44
|
Discovery of a selective M₄ positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia.
|
Bioorg Med Chem Lett
|
2012
|
0.95
|
|
45
|
Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4).
|
Bioorg Med Chem Lett
|
2009
|
0.95
|
|
46
|
Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide (ML254).
|
J Med Chem
|
2013
|
0.95
|
|
47
|
Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.
|
Bioorg Med Chem Lett
|
2012
|
0.94
|
|
48
|
Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics.
|
J Med Chem
|
2015
|
0.94
|
|
49
|
Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode.
|
ACS Chem Neurosci
|
2012
|
0.93
|
|
50
|
mGluR7's lucky number.
|
Proc Natl Acad Sci U S A
|
2006
|
0.93
|
|
51
|
Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375).
|
J Med Chem
|
2013
|
0.92
|
|
52
|
Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu₅).
|
J Med Chem
|
2014
|
0.92
|
|
53
|
Cell-type specific expression of a dominant negative PKA mutation in mice.
|
PLoS One
|
2011
|
0.91
|
|
54
|
Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule.
|
Bioorg Med Chem Lett
|
2012
|
0.90
|
|
55
|
Discovery of 2-(2-benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu₅): from an artificial neural network virtual screen to an in vivo tool compound.
|
ChemMedChem
|
2012
|
0.90
|
|
56
|
Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.
|
Bioorg Med Chem Lett
|
2013
|
0.88
|
|
57
|
A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors.
|
ACS Chem Neurosci
|
2014
|
0.88
|
|
58
|
Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for CNS disorders.
|
Prog Mol Biol Transl Sci
|
2013
|
0.87
|
|
59
|
M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor's location.
|
J Neurosci
|
2014
|
0.87
|
|
60
|
Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor.
|
Bioorg Med Chem Lett
|
2012
|
0.86
|
|
61
|
Melanocyte-lineage expression of Cre recombinase using Mitf regulatory elements.
|
Pigment Cell Melanoma Res
|
2008
|
0.86
|
|
62
|
Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism.
|
Bioorg Med Chem Lett
|
2012
|
0.85
|
|
63
|
Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.
|
Bioorg Med Chem Lett
|
2013
|
0.84
|
|
64
|
Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction.
|
ACS Chem Neurosci
|
2013
|
0.84
|
|
65
|
Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.
|
Bioorg Med Chem Lett
|
2011
|
0.83
|
|
66
|
Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator.
|
Bioorg Med Chem Lett
|
2011
|
0.83
|
|
67
|
Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4).
|
ACS Chem Neurosci
|
2016
|
0.83
|
|
68
|
Heterotropic activation of the midazolam hydroxylase activity of CYP3A by a positive allosteric modulator of mGlu5: in vitro to in vivo translation and potential impact on clinically relevant drug-drug interactions.
|
Drug Metab Dispos
|
2013
|
0.82
|
|
69
|
Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012.
|
Bioorg Med Chem Lett
|
2012
|
0.82
|
|
70
|
Discovery and SAR of a novel series of non-MPEP site mGlu₅ PAMs based on an aryl glycine sulfonamide scaffold.
|
Bioorg Med Chem Lett
|
2012
|
0.82
|
|
71
|
Activation of group II metabotropic glutamate receptors induces long-term depression of excitatory synaptic transmission in the substantia nigra pars reticulata.
|
Neurosci Lett
|
2011
|
0.81
|
|
72
|
Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7.
|
ACS Chem Neurosci
|
2014
|
0.80
|
|
73
|
Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu₄.
|
ACS Comb Sci
|
2011
|
0.80
|
|
74
|
Functional selectivity induced by mGlu₄ receptor positive allosteric modulation and concomitant activation of Gq coupled receptors.
|
Neuropharmacology
|
2012
|
0.80
|
|
75
|
Iterative experimental and virtual high-throughput screening identifies metabotropic glutamate receptor subtype 4 positive allosteric modulators.
|
J Mol Model
|
2012
|
0.80
|
|
76
|
N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats.
|
Bioorg Med Chem Lett
|
2013
|
0.80
|
|
77
|
Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule.
|
Bioorg Med Chem Lett
|
2013
|
0.79
|
|
78
|
Discovery of (S)-2-cyclopentyl-N-((1-isopropylpyrrolidin2-yl)-9-methyl-1-oxo-2,9-dihydro-1H-pyrrido[3,4-b]indole-4-carboxamide (VU0453379): a novel, CNS penetrant glucagon-like peptide 1 receptor (GLP-1R) positive allosteric modulator (PAM).
|
J Med Chem
|
2014
|
0.78
|
|
79
|
Discovery and development of a potent and highly selective small molecule muscarinic acetylcholine receptor subtype I (mAChR 1 or M1) antagonist in vitro and in vivo probe.
|
Curr Top Med Chem
|
2009
|
0.78
|
|
80
|
The metabotropic glutamate receptor 8 agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson's disease.
|
Neuropharmacology
|
2012
|
0.77
|
|
81
|
Development and Antiparkinsonian Activity of VU0418506, a Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor 4 Homomers without Activity at mGlu2/4 Heteromers.
|
ACS Chem Neurosci
|
2016
|
0.76
|
|
82
|
Approaches for probing allosteric interactions at 7 transmembrane spanning receptors.
|
Prog Mol Biol Transl Sci
|
2013
|
0.75
|
|
83
|
MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines.
|
Tetrahedron Lett
|
2009
|
0.75
|
|
84
|
Synthesis and biological characterization of a series of novel diaryl amide M₁ antagonists.
|
Bioorg Med Chem Lett
|
2012
|
0.75
|
|
85
|
Discovery of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A novel negative allosteric modulator of metabotropic glutamate receptor subtype 5 selected for clinical evaluation.
|
J Med Chem
|
2017
|
0.75
|
|
86
|
The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies.
|
Curr Neuropharmacol
|
2016
|
0.75
|
|
87
|
Genetic reduction or negative modulation of mGlu7 does not impact anxiety and fear learning phenotypes in a mouse model of MECP2 Duplication syndrome.
|
ACS Chem Neurosci
|
2017
|
0.75
|