Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

Darren W. Engers; Alice L. Rodriguez; Richard Williams; Alexis S. Hammond; Daryl Venable; Oluwatomi Oluwatola; Gary A. Sulikowski; P. Jeffrey Conn; Craig W. Lindsley

doi:10.1002/cmdc.200800357

Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

Darren W. Engers, Alice L. Rodriguez, Richard Williams, Alexis S. Hammond, Daryl Venable, Oluwatomi Oluwatola, Gary A. Sulikowski, P. Jeffrey Conn, Craig W. Lindsley

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

37 Scopus citations

Abstract

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

Original language	English (US)
Pages (from-to)	505-511
Number of pages	7
Journal	ChemMedChem
Volume	4
Issue number	4
DOIs	https://doi.org/10.1002/cmdc.200800357
State	Published - Apr 17 2009
Externally published	Yes

Keywords

Allosteric modulation
Glutamate receptors
Neurological agents
Structure-activity relationships

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry

Access to Document

10.1002/cmdc.200800357

Cite this

@article{6e59177f552443fca8694ee1aff1dbca,

title = "Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273",

abstract = "An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.",

keywords = "Allosteric modulation, Glutamate receptors, Neurological agents, Structure-activity relationships",

author = "Engers, {Darren W.} and Rodriguez, {Alice L.} and Richard Williams and Hammond, {Alexis S.} and Daryl Venable and Oluwatomi Oluwatola and Sulikowski, {Gary A.} and Conn, {P. Jeffrey} and Lindsley, {Craig W.}",

year = "2009",

month = apr,

day = "17",

doi = "10.1002/cmdc.200800357",

language = "English (US)",

volume = "4",

pages = "505--511",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley and Sons Ltd",

number = "4",

}

TY - JOUR

T1 - Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

AU - Engers, Darren W.

AU - Rodriguez, Alice L.

AU - Williams, Richard

AU - Hammond, Alexis S.

AU - Venable, Daryl

AU - Oluwatola, Oluwatomi

AU - Sulikowski, Gary A.

AU - Conn, P. Jeffrey

AU - Lindsley, Craig W.

PY - 2009/4/17

Y1 - 2009/4/17

N2 - An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

AB - An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

KW - Allosteric modulation

KW - Glutamate receptors

KW - Neurological agents

KW - Structure-activity relationships

UR - http://www.scopus.com/inward/record.url?scp=65549164083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549164083&partnerID=8YFLogxK

U2 - 10.1002/cmdc.200800357

DO - 10.1002/cmdc.200800357

M3 - Article

C2 - 19197923

AN - SCOPUS:65549164083

SN - 1860-7179

VL - 4

SP - 505

EP - 511

JO - ChemMedChem

JF - ChemMedChem

IS - 4

ER -

Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this