Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain

Stephanie Brumfield; Peter Korakas; Lisa S. Silverman; Deen Tulshian; Julius J. Matasi; Li Qiang; Chad E. Bennett; Duane A. Burnett; William J. Greenlee; Chad E. Knutson; Wen Lian Wu; T. K. Sasikumar; Martin Domalski; Rosalia Bertorelli; Mariagrazia Grilli; Gianluca Lozza; Angelo Reggiani; Cheng Li

doi:10.1016/j.bmcl.2012.09.048

Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain

Stephanie Brumfield, Peter Korakas, Lisa S. Silverman, Deen Tulshian, Julius J. Matasi, Li Qiang, Chad E. Bennett, Duane A. Burnett, William J. Greenlee, Chad E. Knutson, Wen Lian Wu, T. K. Sasikumar, Martin Domalski, Rosalia Bertorelli, Mariagrazia Grilli, Gianluca Lozza, Angelo Reggiani, Cheng Li

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.

Lingua originale	Inglese
pagine (da-a)	7223-7226
Numero di pagine	4
Rivista	Bioorganic and Medicinal Chemistry Letters
Volume	22
Numero di pubblicazione	23
DOI	https://doi.org/10.1016/j.bmcl.2012.09.048
Stato di pubblicazione	Pubblicato - 1 dic 2012
Pubblicato esternamente	Sì

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10.1016/j.bmcl.2012.09.048

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Brumfield, S., Korakas, P., Silverman, L. S., Tulshian, D., Matasi, J. J., Qiang, L., Bennett, C. E., Burnett, D. A., Greenlee, W. J., Knutson, C. E., Wu, W. L., Sasikumar, T. K., Domalski, M., Bertorelli, R., Grilli, M., Lozza, G., Reggiani, A., & Li, C. (2012). Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain. Bioorganic and Medicinal Chemistry Letters, 22(23), 7223-7226. https://doi.org/10.1016/j.bmcl.2012.09.048

@article{1587d75456634399a1ef1abc6ed105db,

title = "Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain",

abstract = "High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.",

author = "Stephanie Brumfield and Peter Korakas and Silverman, {Lisa S.} and Deen Tulshian and Matasi, {Julius J.} and Li Qiang and Bennett, {Chad E.} and Burnett, {Duane A.} and Greenlee, {William J.} and Knutson, {Chad E.} and Wu, {Wen Lian} and Sasikumar, {T. K.} and Martin Domalski and Rosalia Bertorelli and Mariagrazia Grilli and Gianluca Lozza and Angelo Reggiani and Cheng Li",

year = "2012",

month = dec,

day = "1",

doi = "10.1016/j.bmcl.2012.09.048",

language = "English",

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pages = "7223--7226",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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Brumfield, S, Korakas, P, Silverman, LS, Tulshian, D, Matasi, JJ, Qiang, L, Bennett, CE, Burnett, DA, Greenlee, WJ, Knutson, CE, Wu, WL, Sasikumar, TK, Domalski, M, Bertorelli, R, Grilli, M, Lozza, G, Reggiani, A & Li, C 2012, 'Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain', Bioorganic and Medicinal Chemistry Letters, vol. 22, n. 23, pagg. 7223-7226. https://doi.org/10.1016/j.bmcl.2012.09.048

TY - JOUR

T1 - Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain

AU - Brumfield, Stephanie

AU - Korakas, Peter

AU - Silverman, Lisa S.

AU - Tulshian, Deen

AU - Matasi, Julius J.

AU - Qiang, Li

AU - Bennett, Chad E.

AU - Burnett, Duane A.

AU - Greenlee, William J.

AU - Knutson, Chad E.

AU - Wu, Wen Lian

AU - Sasikumar, T. K.

AU - Domalski, Martin

AU - Bertorelli, Rosalia

AU - Grilli, Mariagrazia

AU - Lozza, Gianluca

AU - Reggiani, Angelo

AU - Li, Cheng

PY - 2012/12/1

Y1 - 2012/12/1

N2 - High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.

AB - High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.

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U2 - 10.1016/j.bmcl.2012.09.048

DO - 10.1016/j.bmcl.2012.09.048

M3 - Article

SN - 0960-894X

VL - 22

SP - 7223

EP - 7226

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain

Abstract

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