| Rank |
Title |
Journal |
Year |
PubWeight™‹?› |
|
1
|
Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells.
|
J Biol Chem
|
2003
|
1.86
|
|
2
|
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
|
|
3
|
Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor.
|
J Med Chem
|
2010
|
1.40
|
|
4
|
Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.
|
Drug Metab Dispos
|
2005
|
1.34
|
|
5
|
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
|
|
6
|
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
|
|
7
|
Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity.
|
Biol Psychiatry
|
2012
|
1.22
|
|
8
|
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
|
|
9
|
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
|
|
10
|
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
|
|
11
|
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
|
|
12
|
A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation.
|
J Pharmacol Exp Ther
|
2010
|
1.10
|
|
13
|
Discovery of (R)-(2-fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-hydroxypiperidin-1-yl)methanone (ML337), an mGlu3 selective and CNS penetrant negative allosteric modulator (NAM).
|
J Med Chem
|
2013
|
1.10
|
|
14
|
Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics.
|
ACS Chem Biol
|
2014
|
1.09
|
|
15
|
Kinetic and thermodynamic analysis of the hydrolytic ring-opening of the malondialdehyde-deoxyguanosine adduct, 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)- pyrimido[1,2-alpha]purin-10(3H)-one.
|
J Am Chem Soc
|
2004
|
1.08
|
|
16
|
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
|
|
17
|
Selective inhibition of the K(ir)2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR, and pharmacological characterization of ML133.
|
ACS Chem Biol
|
2011
|
1.06
|
|
18
|
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
|
|
19
|
ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice.
|
ACS Chem Neurosci
|
2013
|
1.04
|
|
20
|
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
|
|
21
|
In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M1dG.
|
Proc Natl Acad Sci U S A
|
2006
|
1.04
|
|
22
|
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
|
|
23
|
Kinetics and mechanism of the general-acid-catalyzed ring-closure of the malondialdehyde-DNA adduct, N2-(3-oxo-1-propenyl)deoxyguanosine (N2OPdG-), to 3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin- 10(3H)-one (M1dG).
|
J Am Chem Soc
|
2004
|
1.02
|
|
24
|
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
|
|
25
|
Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener.
|
ACS Chem Neurosci
|
2011
|
0.99
|
|
26
|
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
|
|
27
|
Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib.
|
Mol Cancer Ther
|
2006
|
0.98
|
|
28
|
Enzyme-activated, hypoxia-selective DNA damage by 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxide.
|
Chem Res Toxicol
|
2004
|
0.97
|
|
29
|
Discovery of ML326: The first sub-micromolar, selective M5 PAM.
|
Bioorg Med Chem Lett
|
2013
|
0.97
|
|
30
|
The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease.
|
ACS Chem Neurosci
|
2011
|
0.96
|
|
31
|
DNA strand damage product analysis provides evidence that the tumor cell-specific cytotoxin tirapazamine produces hydroxyl radical and acts as a surrogate for O(2).
|
J Am Chem Soc
|
2007
|
0.96
|
|
32
|
Exocyclic DNA lesions stimulate DNA cleavage mediated by human topoisomerase II alpha in vitro and in cultured cells.
|
Biochemistry
|
2005
|
0.96
|
|
33
|
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
|
|
34
|
Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells.
|
J Med Chem
|
2013
|
0.95
|
|
35
|
Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe.
|
Bioorg Med Chem Lett
|
2012
|
0.95
|
|
36
|
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
|
|
37
|
Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.
|
Bioorg Med Chem Lett
|
2012
|
0.94
|
|
38
|
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
|
|
39
|
Oxidative deboronation of the peptide boronic acid proteasome inhibitor bortezomib: contributions from reactive oxygen species in this novel cytochrome P450 reaction.
|
Chem Res Toxicol
|
2006
|
0.92
|
|
40
|
Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu₅).
|
J Med Chem
|
2014
|
0.92
|
|
41
|
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
|
|
42
|
Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071.
|
Bioorg Med Chem Lett
|
2011
|
0.89
|
|
43
|
Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.
|
Bioorg Med Chem Lett
|
2013
|
0.88
|
|
44
|
Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor.
|
Bioorg Med Chem Lett
|
2012
|
0.86
|
|
45
|
Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.
|
Bioorg Med Chem Lett
|
2013
|
0.84
|
|
46
|
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
|
|
47
|
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.
|
Bioorg Med Chem Lett
|
2013
|
0.83
|
|
48
|
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
|
|
49
|
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
|
|
50
|
Enzymatic conversion of 6-nitroquinoline to the fluorophore 6-aminoquinoline selectively under hypoxic conditions.
|
Chem Res Toxicol
|
2013
|
0.82
|
|
51
|
Development of a method for determination of the malondialdehyde-deoxyguanosine adduct in urine using liquid chromatography-tandem mass spectrometry.
|
Anal Biochem
|
2003
|
0.82
|
|
52
|
Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012.
|
Bioorg Med Chem Lett
|
2012
|
0.82
|
|
53
|
Evaluation of microdosing to assess pharmacokinetic linearity in rats using liquid chromatography-tandem mass spectrometry.
|
Drug Metab Dispos
|
2005
|
0.82
|
|
54
|
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
|
|
55
|
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
|
|
56
|
Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.
|
ACS Chem Neurosci
|
2015
|
0.81
|
|
57
|
Aqueous versus non-aqueous salt delivery strategies to enhance oral bioavailability of a mitogen-activated protein kinase-activated protein kinase (MK-2) inhibitor in rats.
|
J Pharm Sci
|
2009
|
0.81
|
|
58
|
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
|
|
59
|
Discovery of a highly selective PLD2 inhibitor (ML395): a new probe with improved physiochemical properties and broad-spectrum antiviral activity against influenza strains.
|
ChemMedChem
|
2014
|
0.80
|
|
60
|
Thiol-activated DNA damage by α-bromo-2-cyclopentenone.
|
Chem Res Toxicol
|
2011
|
0.79
|
|
61
|
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
|
|
62
|
Utilizing a novel tandem oral dosing strategy to enhance exposure of low-solubility drug candidates in a preclinical setting.
|
J Pharm Sci
|
2010
|
0.78
|
|
63
|
In vitro-in vivo correlation and translation to the clinical outcome for CJ-13,610, a novel inhibitor of 5-lipoxygenase.
|
Drug Metab Dispos
|
2010
|
0.78
|
|
64
|
In vitro metabolism of oxymetazoline: evidence for bioactivation to a reactive metabolite.
|
Drug Metab Dispos
|
2010
|
0.78
|
|
65
|
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
|
|
66
|
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
|
|
67
|
Bioactivation of benzylamine to reactive intermediates in rodents: formation of glutathione, glutamate, and peptide conjugates.
|
Chem Res Toxicol
|
2002
|
0.76
|
|
68
|
Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist.
|
Drug Metab Lett
|
2010
|
0.76
|
|
69
|
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
|
|
70
|
Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere.
|
Bioorg Med Chem Lett
|
2012
|
0.75
|
|
71
|
Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).
|
Bioorg Med Chem Lett
|
2004
|
0.75
|