189192-18-5Relevant articles and documents
Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907
Gilbertson, Scott R.,Chen, Ying-Chu,Soto, Claudia A.,Yang, Yaxing,Rice, Kenner C.,Cunningham, Kathryn A.,Anastasio, Noelle C.
, p. 1381 - 1385 (2018/03/23)
The approach of tethering together two known receptor ligands, to be used as molecular probes for the study of G protein-coupled receptor (GPCR) systems, has proven to be a valuable approach. Selective ligands that possess functionality that can be used to link to other ligands, are useful in the development of novel antagonists and agonists. Such molecules can also be attached to reporter molecules, such as fluorophores, for the study of GPCR dimerization and its role in signaling. The highly selective serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907 (volinanserin) is of clinical interest in the treatment of neurological and mental health disorders. Here, we synthesized the most active (+)-M100907 enantiomer as well as a series of derivatives that possessed either an alkyne or an azide. The triazole resulting from the dipolar cycloaddition of these groups did not interfere with the ability of the bivalent ligand to act as an antagonist. Thus, we have synthesized a number of compounds which will prove useful in elucidating the role of the 5-HT2AR in the central nervous system.
Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
Herth, Matthias M.,Kramer, Vasko,Piel, Markus,Palner, Mikael,Riss, Patrick J.,Knudsen, Gitte M.,Roesch, Frank
experimental part, p. 2989 - 3002 (2009/09/05)
Radiolabelled piperidine derivatives such as [11C]MDL 100907 and [18F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with 18F-fluorine, were synthesized to improve molecular imaging properties of [11C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show Ki-values in the nanomolar range towards the 5-HT2A receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic 18F-tracers for visualization of the 5-HT2A receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have Ki values between 30 and 120 nM. All promising compounds show log P values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of 18F-labelled analogues for 5-HT2A imaging with PET.
A practical synthesis of the serotonin 5-HT(2a) receptor antagonist MDL 100907, its enantiomer and their 3-phenolic derivatives as precursors for [11C ]labeled PET ligands
Ullrich, Thomas,Rice, Kenner C.
, p. 2427 - 2432 (2007/10/03)
A practical synthesis of the 3-phenolic precursor of MDL 100907, a selective 5-HT(2A) receptor antagonist, is described. The route was also applied to the enantiomeric series, thus affording the direct precursors of both 3-[11C]MDL 100907 and its enantiomer as ligands for positron emission tomography. Similar methodology was developed for the direct synthesis of MDL 100907 and its enantiomer, MDL 100009. The routes utilized classical optical resolution of the N-nor intermediates in at least 98% enantiomeric excess and easily afforded multigram amounts of the chiral precursors of a variety of N- and 3-O-substituted enantiomers. Copyright (C) 2000 Elsevier Science Ltd.
An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions
Huang, Yiyun,Mahmood, Khalid,Mathis, Chester A.
, p. 949 - 957 (2007/10/03)
An efficient, integrated route for the synthesis of two precursors of [11C]MDL 100907 labeled in the 2'- or 3'-methoxy position is reported. The synthesis involved a one-pot, two-step process to transform the intermediate esters to ketones and subsequent resolution of the racemic alcohols to their respective enantiomers. The resolved, enantiomerically pure phenol precursors were reacted with high specific activity [11C]methyl iodide to produce [11C]MDL 100907 labeled in two specific positions.
