702-18-1Relevant academic research and scientific papers
Electro-Oxidative Selective Esterification of Methylarenes and Benzaldehydes
Yu, Congjun,?zkaya, Bünyamin,Patureau, Frederic W.
supporting information, p. 3682 - 3687 (2021/02/01)
A mild and green electro-oxidative protocol to construct aromatic esters from methylarenes and alcohols is herein reported. Importantly, the reaction is free of metals, chemical oxidants, bases, acids, and operates at room temperature. Moreover, the design of the electrolyte was found critical for the oxidation state and structure of the coupling products, a rarely documented effect. This electro-oxidative coupling process also displays exceptional tolerance of many fragile easily oxidized functional groups such as hydroxy, aldehyde, olefin, alkyne, as well as neighboring benzylic positions. The enantiomeric enrichment of some chiral alcohols is moreover preserved during this electro-oxidative coupling reaction, making it overall a promising synthetic tool.
18F-Labeled 1,4-Dioxa-8-azaspiro[4.5]decane Derivative: Synthesis and Biological Evaluation of a σ1 Receptor Radioligand with Low Lipophilicity as Potent Tumor Imaging Agent
Xie, Fang,Bergmann, Ralf,Kniess, Torsten,Deuther-Conrad, Winnie,Mamat, Constantin,Neuber, Christin,Liu, Boli,Steinbach, J?rg,Brust, Peter,Pietzsch, Jens,Jia, Hongmei
, p. 5395 - 5407 (2015/08/03)
We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as σ1 receptor ligands. 8-(4-(2-Fluoroethoxy)benzyl)-1,4-dioxa-8-azaspiro[4.5]decane (5a) possessed high affinity (Ki = 5.4 ± 0.4 nM) for σ1 receptors and selectivity for σ2 receptors (30-fold) and the vesicular acetylcholine transporter (1404-fold). [18F]5a was prepared using a one-pot, two-step labeling procedure in an automated synthesis module, with a radiochemical purity of >95%, and a specific activity of 25-45 GBq/μmol. Cellular association, biodistribution, and autoradiography with blocking experiments indicated specific binding of [18F]5a to σ1 receptors in vitro and in vivo. Small animal positron emission tomography (PET) imaging using mouse tumor xenograft models demonstrated a high accumulation in human carcinoma and melanoma. Treatment with haloperidol significantly reduced the accumulation of the radiotracer in tumors. These findings suggest that radiotracer with suitable lipophilicity and appropriate affinity for σ1 receptors could be used for tumor imaging.
Synthesis and evaluation of novel 18F-labeled spirocyclic piperidine derivatives as σ1 receptor ligands for positron emission tomography imaging
Li, Yan,Wang, Xia,Zhang, Jinming,Deuther-Conrad, Winnie,Xie, Fang,Zhang, Xiaojun,Liu, Jian,Qiao, Jinping,Cui, Mengchao,Steinbach, J?rg,Brust, Peter,Liu, Boli,Jia, Hongmei
, p. 3478 - 3491 (2013/06/27)
A series of spirocyclic piperidine derivatives were designed and synthesized as σ1 receptor ligands. In vitro competition binding assays showed that 1′-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2- benzofuran-1,4′-piperidine] (19) possessed high σ1 receptor affinity (Ki = 0.79 nM) and excellent σ1/ σ2 subtype selectivity (350-fold) as well as high σ1/VAChT selectivity (799-fold). The radiolabeled compound [18F]19 was synthesized by substitution of the tosylate precursor 24 with [18F]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/μmol. Biodistribution studies in imprinting control region mice indicated that [ 18F]19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague-Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of σ1 receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [18F]19 to σ1 receptors in vivo.
Synthesis and biological evaluation of 18F labeled fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives for sigma-1 receptor imaging
Wang, Xia,Li, Yan,Deuther-Conrad, Winnie,Xie, Fang,Chen, Xin,Cui, Meng-Chao,Zhang, Xiao-Jun,Zhang, Jin-Ming,Steinbach, J?rg,Brust, Peter,Liu, Bo-Li,Jia, Hong-Mei
, p. 215 - 222 (2013/02/23)
We report the synthesis and evaluation of a series of fluoro-oligo- ethoxylated 4-benzylpiperazine derivatives as potential σ1 receptor ligands. In vitro competition binding assays showed that 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-(2-fluoroethoxy)benzyl)piperazine (6) exhibits low nanomolar affinity for σ1 receptors (Ki = 1.85 ± 1.59 nM) and high subtype selectivity (σ2 receptor: Ki = 291 ± 111 nM; Kiσ2/ Kiσ1 = 157). [18F]6 was prepared in 30-50% isolated radiochemical yield, with radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic 18F- substitution of the corresponding tosylate precursor. The log DpH 7.4 value of [18F]6 was found to be 2.57 ± 0.10, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiotracers in organs known to contain σ1 receptors, including the brain, lungs, kidneys, heart, and spleen. Administration of haloperidol 5 min prior to injection of [18F]6 significantly reduced the concentration of radiotracers in the above-mentioned organs. The accumulation of radiotracers in the bone was quite low suggesting that [18F]6 is relatively stable to in vivo defluorination. The ex vivo autoradiography in rat brain showed high accumulation of radiotracers in the brain areas known to possess high expression of σ1 receptors. These findings suggest that [18F]6 is a suitable radiotracer for imaging σ1 receptors with PET in vivo.
5-Pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis
Kopka, Klaus,Faust, Andreas,Keul, Petra,Wagner, Stefan,Breyholz, Hans-J?rg,H?ltke, Carsten,Schober, Otmar,Sch?fers, Michael,Levkau, Bodo
, p. 6704 - 6715 (2007/10/03)
Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands (CBRs). (S)-5-[1-(2-Methoxymethylpyrrolidinyl) sulfonyl]isatin (7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibition potencies in the nanomolar to subnanomolar range for caspase-3 (Ki = 0.2-56.1 nM). As shown for compound (S)-1-(4-(2-fluoroethoxy) benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.
On the Intermediary Existence of Gaseous Ethylen Fluoronium Ions
Ciommer, Bernhard,Schwarz, Helmut
, p. 635 - 638 (2007/10/02)
The long-sought ethylen fluoronium ion (2) is generated as an intermediate in the dissociative ionization of 1-fluoro-2-(p-methyl)phenoxy ethane (4).However, prior to collisionally induced dissociation 2 undergoes ring-opening, associated with hydrogen migration, to form 1-fluoroethyl cation (3).Other decomposition pathways of the molecular ions of 4 involve (i) direct formation of 3 via a combination of C-O cleavage (loss of ArO(*)) and hydrogen migration (18percent) and (ii) complete positional loss of the α- and β-methylene hydrogen atoms (34percent).The remaining 48percent of the m olecular ions of 4 dissociate via anchimeric assistance of the fluorine in the elimination of ArO(*), thus giving rise to the formation of 2. - Keywords: Fluoronium Ions, Neighbouring Group Participation, Gaseous Ions, Collisional Activation, Mass Spectrometry
