2010
DOI: 10.1021/ml100115a
|View full text |Cite
|
Sign up to set email alerts
|

Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor

Abstract: Novel oxazolobenzimidazoles are described as potent and selective positive allosteric modulators of the metabotropic glutamate receptor 2. The discovery of this class and optimization of its physical and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds (20 and 21) as advanced leads. Compound 20 (TBPCOB) was shown to have robust activity in a PCP-induced hyperlocomotion model in rat, an assay responsive to clinical antipsychotic treatments for schizophrenia.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
2

Citation Types

0
19
0

Year Published

2012
2012
2017
2017

Publication Types

Select...
4
2
2

Relationship

0
8

Authors

Journals

citations
Cited by 25 publications
(19 citation statements)
references
References 26 publications
0
19
0
Order By: Relevance
“…Compound 42 is a representative from this invention with an EC 50 value of 11 nM. Detailed SAR and pharmacological investigation of oxazolobenzimidazoles are described in a separate publication [90]. Optimization of the oxazolidinone through physical and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds, such as compound 43, also known as TBPCOB.…”
Section: Oxazolobenzimidazolesmentioning
confidence: 99%
“…Compound 42 is a representative from this invention with an EC 50 value of 11 nM. Detailed SAR and pharmacological investigation of oxazolobenzimidazoles are described in a separate publication [90]. Optimization of the oxazolidinone through physical and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds, such as compound 43, also known as TBPCOB.…”
Section: Oxazolobenzimidazolesmentioning
confidence: 99%
“…This cyclization locks a co-planar conformation which is suggested to be preferred for mGlu2 receptor PAM activity (Fig. 25) [124]. From the data presented in Merck's patent application, it can be deduced that aryloxymethyl-or heretoaryloxymethyl-groups are largely preferred as substituents at C 2 , with the absolute (S)-configuration at the C 2 stereogenic centre in most cases.…”
Section: Oxazolobenzimidazolesmentioning
confidence: 92%
“…26). An attempt to introduce some polarity and partial basicity in this area of the molecules resulted in the preparation of a subset of pyridyl analogues [124]. The most interesting compound, TBPCOB (68, Fig.…”
Section: Oxazolobenzimidazolesmentioning
confidence: 99%
“…Figure 8 shows the compounds that were reported to have an EC 50 value of less than 30 nM. They are N-aryl-N-(pyridylmethyl)ethanesulfonamides (76) (Barda et al, 2004;Johnson et al, 2003), biphenyl-indanones (77) , 1,4-disubstituted 3-cyanopyridone derivatives (78) (Imogai et al, 2007), 3-(Imidazolyl methyl)-3-azabicyclo[3.1.0]hexan-6-yl)methyl ethers (79 and 80) , oxazolobenzimidazoles (81) (Garbaccio et al, 2010), 3-Benzyl-1,3-oxazolidin-2-ones (82 and 83) (Duplantier et al, 2009), 2-((4-(2-methoxy-4-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)-5,6-dihydro-4H-imidazo[4,5,1-ij][1,7]naphthyridine (84) and THIIC (85) (Fell et al, 2011). Woltering et al, 2008a;Woltering et al, 2008b;Woltering et al, 2010), imidazole derivatives (88) (Gatti McArthur et al, 2006b), pyrazolopyrimidines (89) (Gatti McArthur et al, 2006c), Pyridine and pyrimidine derivatives (90 and 91) (Gatti Mcarthur et al, 2007), acetylenyl-pyrazolo-pyrimidine derivatives (92 and 93) (Gatti McArthur et al, 2006a).…”
Section: Allosteric Modulators For Mglur2mentioning
confidence: 99%