tert-butyl (4-acetylphenyl)(methyl)carbamate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl (4-acetylphenyl)(methyl)carbamate
• 英文别名: tert-butyl N-(4-acetylphenyl)-N-methylcarbamate
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: RFHISWGEKAVKNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-acetylphenyl)(methyl)carbamate 在 ammonium acetate 、 三氟乙酸 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 正丁醇 为溶剂， 反应 22.0h， 生成 (Z)-N-methyl-4-(4-phenyl-5-((3-phenyl-5-(4-(prop-2-yn-1-yloxy)phenyl)-2H-pyrrol-2-ylidene)amino)-1H-pyrrol-2-yl)aniline
  参考文献：
  名称：

  Near-Infrared Photoactivatable Nitric Oxide Donors with Integrated Photoacoustic Monitoring

  摘要：

  Photoacoustic (PA) tomography is a non-invasive technology that utilizes near-infrared (NIR) excitation and ultrasonic detection to image biological tissue at centimeter depths. While several activatable small-molecule PA sensors have been developed for various analytes, the use of PA molecules for deep-tissue analyte delivery and monitoring remains an underexplored area of research. Herein, we describe the synthesis, characterization, and in vivo validation of photoNOD-1 and photoNOD-2, the first organic, NIR-photocontrolled nitric oxide (NO) donors that incorporate a PA readout of analyte release. These molecules consist of an aza-BODIPY dye appended with an aryl N-nitrosamine NO-donating moiety. The photoNODs exhibit chemostability to various biological stimuli, including redox-active metals and CYP450 enzymes, and demonstrate negligible cytotoxicity in the absence of irradiation. Upon single-photon NIR irradiation, photoNOD-1 and photoNOD-2 release NO as well as rNOD-1 or rNOD-2, PA-active products that enable ratiometric monitoring of NO release. Our in vitro studies show that, upon irradiation, photoNOD-1 and photoNOD-2 exhibit 46.6-fold and 21.5-fold ratiometric turn-ons, respectively. Moreover, unlike existing NIR NO donors, the photoNODs do not require encapsulation or multiphoton activation for use in live animals. In this study, we use PA tomography to monitor the local, irradiation-dependent release of NO from photoNOD-1 and photoNOD-2 in mice after subcutaneous treatment. In addition, we use a murine model for breast cancer to show that photoNOD-1 can selectively affect tumor growth rates in the presence of NIR light stimulation following systemic administration.

  DOI：

  10.1021/jacs.8b05514
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 mineral oil 为溶剂， 反应 9.67h， 生成 tert-butyl (4-acetylphenyl)(methyl)carbamate
  参考文献：
  名称：

  具有增强光声特性的刺激响应探针的构象限制 Aza-BODIPY 平台

  摘要：

  光声 (PA) 染料吸收近红外 (NIR) 光以产生超声波信号，可以在厘米深度的组织中检测到，其分辨率明显高于使用基于荧光的方法成像的染料。因此，PA 试剂作为研究活体动物疾病模型的研究工具显示出巨大的前景。然而，可激活的 PA 探针的开发受到了适当的 PA 活性分子平台的相对稀缺性的阻碍，这些平台具有可以以合理方式操纵的特性。在此，我们合成并评估了 aza-BODIPY 染料平台在吸光度、荧光和 PA 特性方面的六种修改。我们确定了一种有前途的构象限制 aza-BODIPY (CRaB) 支架，它优先考虑了设计具有最佳比例 PA 响应的刺激响应染料所需的三个标准：NIR 波长处的吸光度、强 PA 强度和与所需刺激相互作用时的大 Δλ . 使用这种支架，我们合成了三种化学上不同的刺激响应 PA 探针，并证明了体外理论比率响应的 2 到 8 倍改进。这表明 PA 参数的改进是可推广的。最后，我们验证了每个

  DOI：

  10.1021/jacs.9b06694

文献信息

• [EN] NOVEL COMPOUNDS FOR THE DIAGNOSIS, TREATMENT AND PREVENTION OF DISEASES ASSOCIATED WITH THE AGGREGATION OF ALPHA-SYNUCLEIN<br/>[FR] NOUVEAUX COMPOSÉS POUR LE DIAGNOSTIC, LE TRAITEMENT ET LA PRÉVENTION DE MALADIES ASSOCIÉES À L'AGRÉGATION DE L'ALPHA-SYNUCLÉINE
  申请人：MODAG GMBH

  公开号：WO2021099518A1

  公开（公告）日：2021-05-27

  The present invention relates to compounds represented by general formula (la), (lb), (lla) or(llb). These compounds are suitable for imaging alpha-synuclein and for diagnosing diseases which are associated with the aggregation of alpha-synuclein. The compounds are also useful for treating and preventing diseases which are associated with the aggregation of alpha-synuclein.

  本发明涉及由通式(la)、(lb)、(lla)或(llb)表示的化合物。这些化合物适用于成像α-突触核蛋白和诊断与α-突触核蛋白聚集相关的疾病。这些化合物还适用于治疗和预防与α-突触核蛋白聚集相关的疾病。
• A Conformationally Restricted Aza-BODIPY Platform for Stimulus-Responsive Probes with Enhanced Photoacoustic Properties
  作者：Effie Y. Zhou、Hailey J. Knox、Chang Liu、Weili Zhao、Jefferson Chan

  DOI：10.1021/jacs.9b06694

  日期：2019.11.6

  rational manner. Herein we synthesized and evaluated six modifications to the aza-BODIPY dye platform with respect to their absorbance, fluorescence, and PA properties. We identified a promising conformationally restricted aza-BODIPY (CRaB) scaffold that prioritizes three criteria necessary for the design of stimulus-responsive dyes with optimal ratiometric PA response: absorbance at NIR wavelengths, strong

  光声 (PA) 染料吸收近红外 (NIR) 光以产生超声波信号，可以在厘米深度的组织中检测到，其分辨率明显高于使用基于荧光的方法成像的染料。因此，PA 试剂作为研究活体动物疾病模型的研究工具显示出巨大的前景。然而，可激活的 PA 探针的开发受到了适当的 PA 活性分子平台的相对稀缺性的阻碍，这些平台具有可以以合理方式操纵的特性。在此，我们合成并评估了 aza-BODIPY 染料平台在吸光度、荧光和 PA 特性方面的六种修改。我们确定了一种有前途的构象限制 aza-BODIPY (CRaB) 支架，它优先考虑了设计具有最佳比例 PA 响应的刺激响应染料所需的三个标准：NIR 波长处的吸光度、强 PA 强度和与所需刺激相互作用时的大 Δλ . 使用这种支架，我们合成了三种化学上不同的刺激响应 PA 探针，并证明了体外理论比率响应的 2 到 8 倍改进。这表明 PA 参数的改进是可推广的。最后，我们验证了每个
• Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging
  作者：Tetsuro Tago、Shozo Furumoto、Nobuyuki Okamura、Ryuichi Harada、Yoichi Ishikawa、Hiroyuki Arai、Kazuhiko Yanai、Ren Iwata、Yukitsuka Kudo

  DOI：10.1002/jlcr.3133

  日期：2014.1

  Alzheimer's disease (AD) is the most common cause of dementia. Senile plaques, consisting of β-amyloid, and neurofibrillary tangles (NFTs), composed of tau protein, are representative pathological hallmarks of AD. It is believed that the accumulation of NFTs precedes the onset of clinical symptoms of AD and correlates with the progression of memory dysfunction. Thus, the use of noninvasive detection techniques including radiolabeled probes and positron emission tomography (PET) will facilitate early diagnosis or staging of AD. In this study, we synthesized and evaluated novel hydroxylated 2-arylquinoline derivatives as tau imaging PET probes. The binding affinities of compounds for tau were evaluated by fluorescent staining of the AD hippocampal section and a competitive binding assay using [18F]THK-523. THK-951 showed high binding affinity for tau pathology in an AD brain section and K18Δ280K fibrils (Ki = 20.7 nM); thus, we radiosynthesized a 11C-labeled THK-951 and further studied its potential as a tau PET probe. The [11C]THK-951 demonstrated excellent kinetics in a normal mouse brain (3.23% ID/g at 2 min postinjection and 0.15% ID/g at 30 min postinjection) and showed the labeling of NFTs in an AD brain section by autoradiography assay. These findings indicate the availability of [11C]THK-951 for in vivo PET imaging of tau pathology in AD. Copyright © 2013 John Wiley & Sons, Ltd.

  阿尔茨海默病（AD）是导致痴呆症的最常见原因。老年斑（由β-淀粉样蛋白组成）和神经纤维缠结（NFTs，主要由tau蛋白组成）是AD的典型病理特征。研究认为，NFT的积累在临床症状出现之前，并与记忆功能障碍的进展相关。因此，采用包括放射性标记探针和正电子发射断层扫描（PET）在内的非侵入性检测技术将有助于AD的早期诊断或分期。在本研究中，我们合成并评估了新型羟基化2-芳基喹啉衍生物作为tau成像的PET探针。通过对AD海马切片的荧光染色和使用[18F]THK-523的竞争结合实验，评估了化合物与tau的结合亲和力。THK-951在AD脑切片和K18Δ280K纤维中显示出对tau病理的高结合亲和力（Ki = 20.7 nM）；因此，我们放射合成了11C标记的THK-951，并进一步研究其作为tau PET探针的潜力。[11C]THK-951在正常小鼠脑中表现出优良的动力学（注射后2分钟为3.23% ID/g，注射后30分钟为0.15% ID/g），并通过自显影实验显示在AD脑切片中标记了NFT。这些发现表明[11C]THK-951可用于AD中tau病理的体内PET成像。版权 © 2013 John Wiley & Sons, Ltd.
• ¹¹ C Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to α‐Synuclein Fibrils in vitro and Crosses the Blood‐Brain Barrier
  作者：Andreas Maurer、Andrei Leonov、Sergey Ryazanov、Kristina Herfert、Laura Kuebler、Sabrina Buss、Felix Schmidt、Daniel Weckbecker、Ruth Linder、Dirk Bender、Armin Giese、Bernd J. Pichler、Christian Griesinger

  DOI：10.1002/cmdc.201900689

  日期：2020.3.5

  radiosynthesis route for 11 C radiolabeling using in-situ generated [11 C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood-brain barrier and low background

  临床急需对神经退行性疾病中的α-突触核蛋白（αSyn）原纤维（帕金森氏病的标志性生物标志物）进行成像。尽管付出了巨大的努力，但用于αSyn核成像的有希望的示踪剂候选物很少。联苯吡唑是已知的αSyn聚集调节剂，因此具有在体内非侵入性检测该生物标记物的潜力。在这里，我们证明了家族成员anle253b与原纤维αSyn的高亲和力结合，并提出了一种高产位选择性放射合成途径，用于使用原位生成的[11 C]甲醛和还原性甲基化进行11 C放射标记。与大鼠血清体外孵育后，示踪剂的放射-HPLC显示该分子具有出色的稳定性。
• Synthesis of new 1-[4-methane(amino)sulfonylphenyl)]-5-[4-(aminophenyl)]-3-trifluoromethyl-1<i>H</i>-pyrazoles
  作者：Khaled R. A. Abdellatif、Morshed A. Chowdhury、Edward E. Knaus

  DOI：10.1002/jhet.5570450623

  日期：2008.11

  A regiospecific cyclization-dehydration reaction of a 1-[(4-(N-alkyl-N-(tert-butyloxycarbony)amino)-phenyl]-4,4,4-trifluorobutane-1,3-done with a 4-aminosulfonyl-, or 4-methylsulfonyl-, phenylhydrazine hydrochloride in refluxing ethanol proceeded with simultaneous loss of the N-tert-butyloxycarbonyl protecting group to afford a group of 1-(4-methanesulfonylphenyl or 4-aminosulfonylphenyl)-5-[4-(N-

  1-[（4-（N-烷基-N-（叔丁氧基羰基）氨基）-苯基] -4,4,4-三氟丁烷-1,3-done与4-氨基磺酰基的区域特异性环化-脱水反应-或4-甲基磺酰基-苯肼盐酸盐在回流的乙醇中进行，同时失去N-叔丁氧基羰基保护基，得到1-（4-甲磺酰基苯基或4-氨基磺酰基苯基）-5- [4-（N -alkylaminophenyl）] - 3-（三氟甲基）-11 ħ。-pyrazoles（6）随后的吡唑6（的反应- [R 1 = R 2 =具有进行一氧化氮（40 psi）的Me）中经由一个ñ -methylamino- ñ-diazen -1-鎓-1,2-二醇盐中间体，其更基本的二氮烯-1-鎓-1,2-二醇盐的发生质子Ñ 2 -氮，然后硝酰基（HNO）的损失种类，得到的Ñ -亚硝基产物7。