N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu1: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats

Kimberly M. Lovell; Andrew S. Felts; Alice L. Rodriguez; Daryl F. Venable; Hyekyung P. Cho; Ryan D. Morrison; Frank W. Byers; J. Scott Daniels; Colleen M. Niswender; P. Jeffrey Conn; Craig W. Lindsley; Kyle A. Emmitte

doi:10.1016/j.bmcl.2013.05.020

N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu₁: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats

Kimberly M. Lovell, Andrew S. Felts, Alice L. Rodriguez, Daryl F. Venable, Hyekyung P. Cho, Ryan D. Morrison, Frank W. Byers, J. Scott Daniels, Colleen M. Niswender, P. Jeffrey Conn, Craig W. Lindsley, Kyle A. Emmitte

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

10 Scopus citations

Abstract

Development of SAR in an N-acyl-N′-arylpiperazine series of negative allosteric modulators of mGlu₁ using a functional cell-based assay is described in this Letter. Characterization of selected compounds in protein binding assays was used to aid in selecting VU0469650 for further profiling in ancillary pharmacology assays and pharmacokinetic studies. VU0469650 demonstrated an excellent selectivity profile and good exposure in both plasma and brain samples following intraperitoneal dosing in rats.

Original language	English
Pages (from-to)	3713-3718
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2013.05.020
State	Published - 1 Jul 2013

Keywords

Allosteric modulator
CNS
GPCR mGlu
Glutamate
Piperazine

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10.1016/j.bmcl.2013.05.020

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Lovell, K. M., Felts, A. S., Rodriguez, A. L., Venable, D. F., Cho, H. P., Morrison, R. D., Byers, F. W., Daniels, J. S., Niswender, C. M., Conn, P. J., Lindsley, C. W., & Emmitte, K. A. (2013). N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu₁: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats. Bioorganic and Medicinal Chemistry Letters, 23(13), 3713-3718. https://doi.org/10.1016/j.bmcl.2013.05.020

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title = "N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu1: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats",

abstract = "Development of SAR in an N-acyl-N′-arylpiperazine series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. Characterization of selected compounds in protein binding assays was used to aid in selecting VU0469650 for further profiling in ancillary pharmacology assays and pharmacokinetic studies. VU0469650 demonstrated an excellent selectivity profile and good exposure in both plasma and brain samples following intraperitoneal dosing in rats.",

keywords = "Allosteric modulator, CNS, GPCR mGlu, Glutamate, Piperazine",

author = "Lovell, {Kimberly M.} and Felts, {Andrew S.} and Rodriguez, {Alice L.} and Venable, {Daryl F.} and Cho, {Hyekyung P.} and Morrison, {Ryan D.} and Byers, {Frank W.} and Daniels, {J. Scott} and Niswender, {Colleen M.} and Conn, {P. Jeffrey} and Lindsley, {Craig W.} and Emmitte, {Kyle A.}",

year = "2013",

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doi = "10.1016/j.bmcl.2013.05.020",

language = "English",

volume = "23",

pages = "3713--3718",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Lovell, KM, Felts, AS, Rodriguez, AL, Venable, DF, Cho, HP, Morrison, RD, Byers, FW, Daniels, JS, Niswender, CM, Conn, PJ, Lindsley, CW & Emmitte, KA 2013, 'N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu₁: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 13, pp. 3713-3718. https://doi.org/10.1016/j.bmcl.2013.05.020

N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu₁ : Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats. / Lovell, Kimberly M.; Felts, Andrew S.; Rodriguez, Alice L. et al.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 13, 01.07.2013, p. 3713-3718.

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

TY - JOUR

T1 - N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu1

T2 - Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats

AU - Lovell, Kimberly M.

AU - Felts, Andrew S.

AU - Rodriguez, Alice L.

AU - Venable, Daryl F.

AU - Cho, Hyekyung P.

AU - Morrison, Ryan D.

AU - Byers, Frank W.

AU - Daniels, J. Scott

AU - Niswender, Colleen M.

AU - Conn, P. Jeffrey

AU - Lindsley, Craig W.

AU - Emmitte, Kyle A.

PY - 2013/7/1

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KW - CNS

KW - GPCR mGlu

KW - Glutamate

KW - Piperazine

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JO - Bioorganic and Medicinal Chemistry Letters

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IS - 13

ER -

N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu₁: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats

Abstract

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