Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

Richard Williams; J.T. Manka; A.L. Rodriguez; P.N. Vinson; C.M. Niswender; C.D. Weaver; C.K. Jones; P.J. Conn; C.W. Lindsley; S.R. Stauffer

doi:10.1016/j.bmcl.2011.01.044

Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

Richard Williams, J.T. Manka, A.L. Rodriguez, P.N. Vinson, C.M. Niswender, C.D. Weaver, C.K. Jones, P.J. Conn, C.W. Lindsley, S.R. Stauffer

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

36 Citations (Scopus)

Abstract

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. 'Molecular switches' were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents. Published by Elsevier Ltd.

Original language	English
Pages (from-to)	1350-1353
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2011.01.044
Publication status	Published - 01 Mar 2011

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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Williams, R., Manka, J. T., Rodriguez, A. L., Vinson, P. N., Niswender, C. M., Weaver, C. D., Jones, C. K., Conn, P. J., Lindsley, C. W., & Stauffer, S. R. (2011). Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. Bioorganic & Medicinal Chemistry Letters, 21(5), 1350-1353. https://doi.org/10.1016/j.bmcl.2011.01.044

Williams, Richard ; Manka, J.T. ; Rodriguez, A.L. ; Vinson, P.N. ; Niswender, C.M. ; Weaver, C.D. ; Jones, C.K. ; Conn, P.J. ; Lindsley, C.W. ; Stauffer, S.R. / Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. In: Bioorganic & Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 5. pp. 1350-1353.

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author = "Richard Williams and J.T. Manka and A.L. Rodriguez and P.N. Vinson and C.M. Niswender and C.D. Weaver and C.K. Jones and P.J. Conn and C.W. Lindsley and S.R. Stauffer",

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Williams, R, Manka, JT, Rodriguez, AL, Vinson, PN, Niswender, CM, Weaver, CD, Jones, CK, Conn, PJ, Lindsley, CW & Stauffer, SR 2011, 'Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold', Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 5, pp. 1350-1353. https://doi.org/10.1016/j.bmcl.2011.01.044

Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. / Williams, Richard; Manka, J.T.; Rodriguez, A.L.; Vinson, P.N.; Niswender, C.M.; Weaver, C.D.; Jones, C.K.; Conn, P.J.; Lindsley, C.W.; Stauffer, S.R.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 21, No. 5, 01.03.2011, p. 1350-1353.

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

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