3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu 5: Identification of easily prepared tool compounds with CNS exposure in rats

Andrew S. Felts; Stacey R. Lindsley; Jeffrey P. Lamb; Alice L. Rodriguez; Usha N. Menon; Satyawan Jadhav; Carrie K. Jones; P. Jeffrey Conn; Craig W. Lindsley; Kyle A. Emmitte

doi:10.1016/j.bmcl.2010.06.064

3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu ₅: Identification of easily prepared tool compounds with CNS exposure in rats

Andrew S. Felts, Stacey R. Lindsley, Jeffrey P. Lamb, Alice L. Rodriguez, Usha N. Menon, Satyawan Jadhav, Carrie K. Jones, P. Jeffrey Conn, Craig W. Lindsley, Kyle A. Emmitte

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu ₅ using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples.

Original language	English
Pages (from-to)	4390-4394
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2010.06.064
State	Published - 1 Aug 2010

Keywords

Addiction
Allosteric modulator
CNS
Fragile X syndrome
GERD
GPCR
PD-LID
mGlu5

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10.1016/j.bmcl.2010.06.064

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Felts, A. S., Lindsley, S. R., Lamb, J. P., Rodriguez, A. L., Menon, U. N., Jadhav, S., Jones, C. K., Conn, P. J., Lindsley, C. W., & Emmitte, K. A. (2010). 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu ₅: Identification of easily prepared tool compounds with CNS exposure in rats. Bioorganic and Medicinal Chemistry Letters, 20(15), 4390-4394. https://doi.org/10.1016/j.bmcl.2010.06.064

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title = "3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu 5: Identification of easily prepared tool compounds with CNS exposure in rats",

abstract = "Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu 5 using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples.",

keywords = "Addiction, Allosteric modulator, CNS, Fragile X syndrome, GERD, GPCR, PD-LID, mGlu5",

author = "Felts, {Andrew S.} and Lindsley, {Stacey R.} and Lamb, {Jeffrey P.} and Rodriguez, {Alice L.} and Menon, {Usha N.} and Satyawan Jadhav and Jones, {Carrie K.} and Conn, {P. Jeffrey} and Lindsley, {Craig W.} and Emmitte, {Kyle A.}",

year = "2010",

month = aug,

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doi = "10.1016/j.bmcl.2010.06.064",

language = "English",

volume = "20",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Felts, AS, Lindsley, SR, Lamb, JP, Rodriguez, AL, Menon, UN, Jadhav, S, Jones, CK, Conn, PJ, Lindsley, CW & Emmitte, KA 2010, '3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu ₅: Identification of easily prepared tool compounds with CNS exposure in rats', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 15, pp. 4390-4394. https://doi.org/10.1016/j.bmcl.2010.06.064

3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu ₅ : Identification of easily prepared tool compounds with CNS exposure in rats. / Felts, Andrew S.; Lindsley, Stacey R.; Lamb, Jeffrey P. et al.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 15, 01.08.2010, p. 4390-4394.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu 5

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AU - Felts, Andrew S.

AU - Lindsley, Stacey R.

AU - Lamb, Jeffrey P.

AU - Rodriguez, Alice L.

AU - Menon, Usha N.

AU - Jadhav, Satyawan

AU - Jones, Carrie K.

AU - Conn, P. Jeffrey

AU - Lindsley, Craig W.

AU - Emmitte, Kyle A.

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KW - Allosteric modulator

KW - CNS

KW - Fragile X syndrome

KW - GERD

KW - GPCR

KW - PD-LID

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ER -

3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu ₅: Identification of easily prepared tool compounds with CNS exposure in rats

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