Re-exploration of the PHCCC scaffold: Discovery of improved positive allosteric modulators of mGluR4

Richard Williams; Ya Zhou; Colleen M. Niswender; Qingwei Luo; P. Jeffrey Conn; Craig W. Lindsley; Corey R. Hopkins

doi:10.1021/cn9000318

Re-exploration of the PHCCC scaffold: Discovery of improved positive allosteric modulators of mGluR4

Richard Williams, Ya Zhou, Colleen M. Niswender, Qingwei Luo, P. Jeffrey Conn, Craig W. Lindsley, Corey R. Hopkins

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

48 Scopus citations

Abstract

This paper describes a detailed structure-activity relationship (SAR) analysis of the metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulator, (-)-N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes.

Original language	English (US)
Pages (from-to)	411-419
Number of pages	9
Journal	ACS Chemical Neuroscience
Volume	1
Issue number	6
DOIs	https://doi.org/10.1021/cn9000318
State	Published - Jun 16 2010
Externally published	Yes

Keywords

Allosteric modulation
Metabotropic glutamate receptor 4
PHCCC
Parkinson's disease
Positive allosteric modulator
SAR
Structure-activity relationship

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

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abstract = "This paper describes a detailed structure-activity relationship (SAR) analysis of the metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulator, (-)-N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes.",

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AU - Luo, Qingwei

AU - Conn, P. Jeffrey

AU - Lindsley, Craig W.

AU - Hopkins, Corey R.

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AB - This paper describes a detailed structure-activity relationship (SAR) analysis of the metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulator, (-)-N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes.

KW - Allosteric modulation

KW - Metabotropic glutamate receptor 4

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KW - Parkinson's disease

KW - Positive allosteric modulator

KW - SAR

KW - Structure-activity relationship

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Re-exploration of the PHCCC scaffold: Discovery of improved positive allosteric modulators of mGluR4

Abstract

Keywords

ASJC Scopus subject areas

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