Synthesis, SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago-potentiator ADX-47273

被引：33

作者：

Engers, Darren W. ^{[1
]}

Rodriguez, Alice L. ^{[1
]}

Williams, Richard ^{[1
]}

Hammond, Alexis S. ^{[2
]}

Venable, Daryl ^{[1
]}

Oluwatola, Oluwatomi ^{[3
]}

Sulikowski, Gary A. ^{[3
]}

Conn, P. Jeffrey ^{[1
]}

Lindsley, Craig W. ^{[1
,3
]}

机构：

[1] Vanderbilt Univ, Dept Pharmacol, Vanderbilt Program Drug Discovery, Med Ctr,MRBIV Langford 12415D, Nashville, TN 37232 USA

[2] Meharry Med Coll, Neurosci Program, Nashville, TN 37208 USA

[3] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA

来源：

CHEMMEDCHEM | 2009年 / 4卷 / 04期

关键词：

glutamate receptors; allosteric modulation; neurological agents; structure-activity relationships; POSITIVE ALLOSTERIC MODULATORS; GLUTAMATE-RECEPTOR SUBTYPE-5; HIGH-DOSE GLYCINE; NEGATIVE SYMPTOMS; ANTIPSYCHOTIC-LIKE; DOPAMINE; SCHIZOPHRENIA; OCCUPANCY; CLOZAPINE; DISCOVERY;

D O I：

10.1002/cmdc.200800357

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：505 / 511

页数：7

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