329205-68-7Relevant articles and documents
Physical and crystallographic characterisation of the mGlu5 antagonist MTEP and its monohydrochloride
McIldowie, Matthew J.,Gandy, Michael N.,Skelton, Brian W.,Brotchie, Jonathan M.,Koutsantonis, George A.,Spackman, Mark A.,Piggott, Matthew J.
, p. 234 - 245 (2010)
An improved medium scale synthesis of 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]pyridine (MTEP), a selective and potent metabotropic glutamate subtype 5 (mGlu5) antagonist, has allowed thorough characterisation of the crystal structures of the free base and the previously unreported hydrochloride (MTEP.HCl). Hirshfeld surface analysis has revealed that molecules in crystalline MTEP are weakly polar, and aggregate through nonclassical C-H...N hydrogen bonds. A strong ionic N-H+...Cl - hydrogen bond dominates the crystal packing in MTEP.HCl. Despite significant differences in the crystal packing, the molecular structures of MTEP and MTEP.HCl are very similar. The acid dissociation constants for MTEP were investigated using 1H NMR spectroscopy. The second acid dissociation constant (pKa2), associated with the pyridine nitrogen, was determined to be 3.40±0.01, whilst pKa1, associated with the thiazole nitrogen, was estimated to be 0.2. The low pKa values make it unlikely that MTEP is protonated in its biologically active form.
5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3′-bipyridine: A highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity
Roppe, Jeffrey R.,Wang, Bowei,Huang, Dehua,Tehrani, Lida,Kamenecka, Theodore,Schweiger, Edwin J.,Anderson, Jeffery J.,Brodkin, Jesse,Jiang, Xiaohui,Cramer, Merryl,Chung, Janice,Reyes-Manalo, Grace,Munoz, Benito,Cosford, Nicholas D. P.
, p. 3993 - 3996 (2004)
Structure-activity relationship studies leading to the discovery of a new, orally active mGlu5 receptor antagonist are described. The title compound, 5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-2,3′-bipyridine, is highly potent in vitro, has good in vivo recep
Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol- 4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications
Iso, Yasuyoshi,Grajkowska, Ewa,Wroblewski, Jarda T.,Davis, Jared,Goeders, Nicholas E.,Johnson, Kenneth M.,Sanker, Subramaniam,Roth, Bryan L.,Tueckmantel, Werner,Kozikowski, Alan P.
, p. 1080 - 1100 (2007/10/03)
Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.
3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity
Cosford, Nicholas D. P.,Tehrani, Lida,Roppe, Jeffrey,Schweiger, Edwin,Smith, Nicholas D.,Anderson, Jeffrey,Bristow, Linda,Brodkin, Jesse,Jiang, Xiaohui,McDonald, Ian,Rao, Sara,Washburn, Mark,Varney, Mark A.
, p. 204 - 206 (2007/10/03)
2-Methyl-6-(phenylethynyl)pyridine (3), a potent noncompetitive mGlu5 receptor antagonist widely used to characterize the pharmacology of mGlu5 receptors, suffers from a number of shortcomings as a therapeutic agent, including off-target activity and poor
