107151-62-2Relevant academic research and scientific papers
Syntheses and evaluation of a homologous series of aza-vesamicol as improved radioiodine-labeled probes for sigma-1 receptor imaging
Ogawa, Kazuma,Masuda, Ryohei,Mishiro, Kenji,Wang, Mengfei,Kozaka, Takashi,Shiba, Kazuhiro,Kinuya, Seigo,Odani, Akira
, p. 1990 - 1996 (2019)
Sigma-1 receptor imaging probes for determining the expression levels are desirable for diagnoses of various diseases and companion diagnoses of therapeutic agents targeting the sigma-1 receptor. In this study, we aimed to develop probes with higher affin
Selective, Catalytic, and Dual C(sp3)-H Oxidation of Piperazines and Morpholines under Transition-Metal-Free Conditions
Chamorro-Arenas, Delfino,Osorio-Nieto, Urbano,Quintero, Leticia,Hernández-García, Luís,Sartillo-Piscil, Fernando
, p. 15333 - 15346 (2019/01/03)
By using cheap and innocuous reagents, such as NaClO2, NaOCl, and catalytic amounts of TEMPO, a new environmentally friendly protocol for the selective and catalytic TEMPO C(sp3)-H oxidation of piperazines and morpholines to 2,3-diketopiperazines (2,3-DKP) and 3-morpholinones (3-MPs), respectively, has been developed. This novel direct access to 2,3-DKP from piperazines provides significant advantages over the traditional N-monoacylation/intramolecular C-N cyclization procedure. Additionally, by modulating the amounts of TEMPO, 2-alkoxyamino-3-morpholinone can be prepared from morpholine derivatives, which would enable further functionalization at the C2 position of the morpholine skeleton.
New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter - A critical examination of the lead structure
Barthel, Claudia,Sorger, Dietlind,Deuther-Conrad, Winnie,Scheunemann, Matthias,Schweiger, Stephanie,J?ckel, Petra,Roghani, Ali,Steinbach, J?rg,Schüürmann, Gerrit,Sabri, Osama,Brust, Peter,Wenzel, Barbara
, p. 50 - 67 (2015/06/22)
To verify vesamicol as lead structure in the development of radioligands for imaging of VAChT in the brain by PET, we systematically modified this molecule and investigated four different groups of derivatives. Structural changes were conducted in all three ring systems A, B, and C resulting in a library of different vesamicol analogs. Based on their in vitro binding affinity toward VAChT as well as σ1 and σ2 receptors, we performed a structure-affinity relationship (SAR) study regarding both affinity and selectivity. The compounds possessed VAChT affinities in the range of 1.32 nM (benzovesamicol) to >10 mM and selectivity factors from 0.1 to 73 regarding σ1 and σ2 receptors, respectively. We could confirm the exceptional position of benzovesamicols as most affine VAChT ligands. However, we also observed that most of the compounds with high VAChT affinity demonstrated considerable affinity in particular to the σ1 receptor. Finally, none of the various vesamicol analogs in all four groups showed an in vitro binding profile suitable for specific VAChT imaging in the brain.
In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)
Labrie, Philippe,Maddaford, Shawn P.,Lacroix, Jacques,Catalano, Concettina,Lee, David K.H.,Rakhit, Suman,Gaudreault, Rene C.
, p. 3854 - 3868 (2008/02/13)
Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group betw
Synthesis, in Vitro Acetylcholine-Storage-Blocking Activities, and Biological Properties of Derivatives and Analogues of trans-2-(4-Phenylpiperidino)cyclohexanol (Vesamicol)
Rogers, Gary A.,Parsons, Stanley M.,Anderson, D. C.,Nilsson, Lena M.,Bahr, Ben A.,et al.
, p. 1217 - 1230 (2007/10/02)
Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ.The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol.The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography.The absolute configuration of (-)-vesamicol is 1R,2R.Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue.Alterations to all three rings can have large effects on potency.Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency.A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications.A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.
