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. 2011 Mar 14;13(2):159-65.
doi: 10.1021/co1000508. Epub 2011 Feb 21.

Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu₄

Yiu-Yin Cheung  1 , Rocio Zamorano, Anna L Blobaum, C David Weaver, P Jeffrey Conn, Craig W Lindsley, Colleen M Niswender, Corey R Hopkins
Affiliations

Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu₄

Yiu-Yin Cheung et al. ACS Comb Sci. .

Abstract

Using a functional high-throughput screening (HTS) and subsequent solution-phase parallel synthesis approach, we have discovered a novel series of positive allosteric modulators for mGlu₄, a G-protein coupled receptor. This series is comprised of a homopiperazine central core. The solution-phase parallel synthesis and SAR of analogs derived from this series will be presented. This series of positive allosteric modulators of mGlu₄ provide critical research tools to further probe the mGlu₄-mediated effects in Parkinson's disease.

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Figures

Figure 1
Figure 1
Structures of PHCCC, 1, and other recently reported mGlu4 PAMs, 2–9.
Figure 2
Figure 2
Areas of SAR Exploration of VU0105737, 9.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Synthetic procedure for the initial homopiperazine analogs, 20a–j.
Scheme 3
Scheme 3
See this image and copyright information in PMC

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