67980-77-2Relevant articles and documents
Dopamine D4 ligands and models of receptor activation: 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole and related heteroarylmethylarylpiperazines exhibit a substituent effect responsible for additional efficacy tuning.
Stewart, Andrew O,Cowart, Marlon D,Moreland, Robert B,Latshaw, Steve P,Matulenko, Mark A,Bhatia, Pramila A,Wang, Xueqing,Daanen, Jerome F,Nelson, Sherry L,Terranova, Marc A,Namovic, Marian T,Donnelly-Roberts, Diana L,Miller, Loan N,Nakane, Masaki,Sullivan, James P,Brioni, Jorge D
, p. 2348 - 2355 (2004)
A series of subtype selective dopamine D(4) receptor ligands from the hetroarylmethylphenylpiperazine class have been discovered that exhibit a remarkable structure-activity relationship (SAR), revealing a substituent effect in which regiosubstitution on the terminal arylpiperazine ring can modulate functional or intrinsic activity. Other structure-dependent efficacy studies in the dopamine D(4) field have suggested a critical interaction of the heteroarylmethyl moiety with specific protein microdomains in controlling intrinsic activity. Our studies indicate that for some binding orientations, the phenylpiperazine moiety also plays a key role in determining efficacy. These data also implicate a kinetic or efficiency term, contained within measured functional affinities for agonists, which support a sequential binding and conformational stabilization model for receptor activation. The structural similarity between partial agonist and antagonist, within this subset of ligands, and lack of bioisosterism for this substituent effect are key phenomena for these hypotheses.
Exploration of the molecular architecture of the orthosteric binding site in the α4β2 nicotinic acetylcholine receptor with analogs of 3-(dimethylamino)butyl dimethylcarbamate (DMABC) and 1-(pyridin-3-yl)-1,4-diazepane
Bach, Tinna B.,Jensen, Anders A.,Petersen, Jette G.,S?rensen, Troels E.,Della Volpe, Serena,Liu, Jun,Blaazer, Antoni R.,Van Muijlwijk-Koezen, Jacqueline E.,Balle, Thomas,Fr?lund, Bente
, p. 425 - 444 (2015/09/01)
X-ray crystal structures of acetylcholine binding proteins (AChBPs) have revealed two different possible extensions to the classical ligand binding pocket known to accommodate various nicotinic agonists. One of the pockets is limited in size while the oth
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Paragraph 0234, (2013/06/05)
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.