2,2-diphenylbenzo[d][1,3]dioxole-4-carboxylic acid | 54888-41-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,2-diphenylbenzo[d][1,3]dioxole-4-carboxylic acid
• 英文别名: 2,2-Diphenyl-2H-1,3-benzodioxole-4-carboxylic acid；2,2-diphenyl-1,3-benzodioxole-4-carboxylic acid
• CAS: 54888-41-4
• 化学式: C₂₀H₁₄O₄
• 分子量: 318.329
• InChiKey: NHAGERIKBKUEDT-UHFFFAOYSA-N

物化性质

• 熔点：
  188-189 °C(Solv: isopropyl ether (108-20-3); methanol (67-56-1))
• 沸点：
  493.9±45.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-diphenylbenzo[d][1,3]dioxole-4-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 以78%的产率得到2,3-(Diphenylmethylendioxy)-benzoylchlorid
  参考文献：
  名称：

  螯合蛋白系统对四价锆和Thor的工程识别：向灵活的放射治疗和成像平台迈进

  摘要：

  靶向α疗法具有作为癌症治疗的巨大潜力：它提供了向靶细胞传递高细胞毒性剂量的可能性，同时最大程度地减少了对周围健康组织的损害。产生金属α的放射性同位素225 Ac和227 Th是有前途的放射性核素，可用于治疗，可提供足够的螯合和靶向作用。在这里，我们展示了一个新的螯合平台，该平台由与哺乳动物蛋白siderocalin结合的多齿高亲和力供氧配体3,4,3-LI（CAM）组成。各自稳定常数β日志110 = 29.65±0.65，57.26±0.20，和47.71±0.08，对于铕确定III（镧系元素替代为AC III），锆IV，和Th3,4,3-LI（CAM）的IV络合物通过分光光度滴定法显示，该配体是在生理pH值下三价和四价金属离子最强大的螯合剂之一。生成的金属-配体配合物也被铁载体结合蛋白铁德罗林以极高的亲和力识别，其解离常数低于40 nM，并具有紧密的静电相互作用，如Zr IV的蛋白质：配

  DOI：

  10.1021/acs.inorgchem.6b02041
• 作为产物：
  描述：

  二氯二苯甲烷 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 25.0h， 生成 2,2-diphenylbenzo[d][1,3]dioxole-4-carboxylic acid
  参考文献：
  名称：

  Platform to Discover Protease-Activated Antibiotics and Application to Siderophore–Antibiotic Conjugates

  摘要：

  Here we present a platform for discovery of protease-activated prodrugs and apply it to antibiotics that target Gram-negative bacteria. Because cleavable linkers for prodrugs had not been developed for bacterial proteases, we used substrate phage to discover substrates for proteases found in the bacterial periplasm. Rather than focusing on a single protease, we used a periplasmic extract of E. coli to find sequences with the greatest susceptibility to the endogenous mixture of periplasmic proteases. Using a fluorescence assay, candidate sequences were evaluated to identify substrates that release native amine-containing payloads. We next designed conjugates consisting of (1) an N-terminal siderophore to facilitate uptake, (2) a protease-cleavable linker, and (3) an amine-containing antibiotic. Using this strategy, we converted daptomycin-which by itself is active only against Gram-positive bacteria-into an antibiotic capable of targeting Gram-negative Acinetobacter species. We similarly demonstrated siderophore-facilitated delivery of oxazolidinone and macrolide antibiotics into a number of Gram-negative species. These results illustrate this platform's utility for development of protease-activated prodrugs, including Trojan horse antibiotics.

  DOI：

  10.1021/jacs.0c06987

文献信息

• New COMT inhibitors for the treatment of depression and impaired cognition
  申请人：Diederich Francois

  公开号：US20050137162A1

  公开（公告）日：2005-06-23

  The present invention relates to compounds of formula I wherein R 1 is as defined in the specification and to esters thereof which are hydrolyzable under physiological conditions and to the pharmaceutically acceptable salts thereof. The compounds of the invention are inhibitors of COMT and, thus, are useful for the treatment of diseases for which COMT inhibition is beneficial. The invention further relates to the treatment, control, or prevention of diseases such as depression, schizophrenia, Parkinson's disease, and to improve cognition.

  本发明涉及以下式I的化合物 其中R 1 如规范中定义 以及在生理条件下可水解的酯及其药用可接受的盐。本发明的化合物是COMT的抑制剂，因此对于COMT抑制有益的疾病的治疗是有用的。本发明还涉及治疗、控制或预防抑郁症、精神分裂症、帕金森病以及改善认知的疾病。
• Synthesis and Biological Evaluation of Potent Bisubstrate Inhibitors of the Enzyme CatecholO-Methyltransferase (COMT) Lacking a Nitro Group
  作者：Ralph Paulini、Christian Lerner、François Diederich、Roland Jakob-Roetne、Gerhard Zürcher、Edilio Borroni

  DOI：10.1002/hlca.200690179

  日期：2006.9

  activity despite the lack of a NO2 substituent on the catechol moiety. Their synthesis takes advantage of a convergent approach, in which a series of functionalized catechol intermediates is prepared (Schemes 2–7) and coupled to a common adenosine-derived allylic amine building block (Scheme 8). Biological activities of the newly synthesized inhibitors, determined by in vitro enzymatic assay and kinetic

  抑制儿茶酚O-甲基转移酶（COMT）代表了一种可行的策略，可调节儿茶酚胺神经递质或其前体的分解代谢，并且在帕金森氏病的治疗中引起了极大的兴趣。本文中，我们报道了由硝基取代的配体1（K i  = 28 nM，表1）衍生的新一代有效的COMT双底物抑制剂的开发，尽管邻苯二酚上没有NO 2取代基，该抑制剂仍具有很高的生物活性。部分。它们的合成利用会聚方法的优势，其中制备了一系列功能化的邻苯二酚中间体（方案2–7））并偶联至常见的腺苷衍生的烯丙基胺结构单元（方案8）。通过体外酶促测定和动力学研究确定的新合成抑制剂的生物活性清楚地表明，双底物抑制剂的高抑制能力与邻苯二酚OH基团的p K a不相关。发现通过联芳基型连接与邻苯二酚连接的芳族残基最大程度地受益于与该酶的其他有利疏水相互作用，因此是1中NO 2基团的优选替代物。竞争性动力学抑制机制（图2）相对于所述辅因子结合位点被证实在所有情况下，支撑用于抑制剂双底物抑制模式2
• Diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester: a convenient catechol precursor in the synthesis of siderophore vectors suitable for antibiotic Trojan horse strategies
  作者：Etienne Baco、Françoise Hoegy、Isabelle J. Schalk、Gaëtan L. A. Mislin

  DOI：10.1039/c3ob41990h

  日期：——

  Catechols are components of many metal-chelating compounds, including siderophores that are naturally occurring iron(III) chelators excreted by microorganisms. Catechol derivatives are poorly soluble in organic media and the synthesis of catechol-containing molecules requires the use of protected catechol precursors with improved organic solubility. We therefore developed 2,2-diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester. This activated ester reacts with an amine functionalized scaffold to generate chelators in which the catechol functions are protected in the form of diphenyl-benzodioxole moieties. The catechol can subsequently be deprotected, at the end of the synthesis, with trifluoroacetic acid (TFA). This strategy was applied to the synthesis of two catechol compounds functionalized with a terminal propargyl extension. These two compounds were shown to promote iron uptake in Escherichia coli and Pseudomonas aeruginosa. These two compounds are suitable for use as vectors in antibiotic Trojan horse approaches, as they could be conjugated with azide-functionalized antibiotics using the Huisgen dipolar 1,3-cycloaddition.

  儿茶酚是许多金属螯合物的成分，包括由微生物分泌的天然存在的铁(III)螯合剂——侧胞素。儿茶酚衍生物在有机介质中溶解性差，合成含儿茶酚的分子需要使用具有更好有机溶解性的保护儿茶酚前体。因此，我们开发了2,2-二苯基-苯并[1,3]二噁烷-4-羧酸五氟苯酯。这种活化酯可以与一种氨基功能化的骨架反应，生成在二苯基-苯并二噁烷基团形式下保护的儿茶酚功能团。合成结束时，儿茶酚可以通过三氟乙酸（TFA）去保护。该策略用于合成两种带有末端炔基扩展的儿茶酚化合物。这两种化合物被证明能促进大肠杆菌和铜绿假单胞菌对铁的摄取。这两种化合物适合用作抗生素特洛伊木马方法中的载体，因为它们可以通过胡根偶极体1,3-环加成与叠氮功能化抗生素结合。
• New polycyclic β-lactams. Synthesis of 2a,3-dihydroazeto[1,2-a]quinoline-1,4(2H)-diones, structural analogues of the carbacephalosporin antibiotics
  作者：Mario D. Bachi、Joseph Klein

  DOI：10.1039/p19830001925

  日期：——

  dihydroxydihydroazeto[1,2-a]quinoline-1,4(2H)-diones (1). The synthesis involved, as a key step, the completion of the polycyclic β-lactam system by a modified Bischler–Napieralski reaction. It was illustrated by the synthesis of (±)-7,8-dihydroxy-3,3-dimethyl-2-phenoxyacetamido-2a,3-dihydroazeto[1,2-a]quinoline-1,4(2H)-dione (20), which is structurally related to the carbacephalosporin antibiotics.

  已经开发了一种制备二羟基二氢氮杂[1,2 - a ]喹啉-1,4（2H）-二酮（1）的方法。作为关键步骤，合成过程涉及通过修饰的Bischler-Napieralski反应完成多环β-内酰胺系统。通过（±）-7,8-二羟基-3,3-二甲基-2-苯氧基乙酰胺基-2a，3-二氢氮杂并[1,2 - a ]喹啉-1,4（2 H）-二酮的合成说明了这一点。（20），其在结构上与氨基头孢菌素抗生素有关。
• Combinatorial design of multimeric chelating peptoids for selective metal coordination
  作者：Abel Ricano、Ilya Captain、Korey P. Carter、Bryan P. Nell、Gauthier J.-P. Deblonde、Rebecca J. Abergel

  DOI：10.1039/c9sc01068h

  日期：——

  catecholamide chelating units linked via an ethylenediamine bridge and, for comparison, we also synthesized the corresponding mixed ligands derived from the spermine scaffold: 3,4,3-LI(1,2-HOPO)2(CAM)2 and 3,4,3-LI(CAM)2(1,2-HOPO)2. Coordination-based luminescence studies were carried out with Eu3+ and Tb3+ to begin probing the properties of the new ligand architecture and revealed higher sensitization

  当前的金属螯合方法通常基于多齿有机配体，其是通过繁琐的多步合成过程生成的，这些合成过程缺乏系统地改变金属结合基序的灵活性。已知在精胺支架上结合了羟基吡啶酮或邻苯二甲酰胺结合部分的八齿配体显示出一些对f元素的最高亲和力。然而，增强对特定镧系离子或act系离子的结合亲和力，需要允许模块化和高通量合成的配体结构。在这里，我们介绍了一个高通量的组合库，该库包含16个四聚N-取代的甘氨酸低聚物（类肽），它们包含通过连接的羟基吡啶酮或儿茶酚酰胺螯合单元乙二胺桥，作为比较，我们还合成了相应的混合精胺支架配体：3,4,3-LI（1,2-HOPO）2（CAM）2和3,4,3-LI（CAM） ）2（1,2-HOPO）2。用Eu 3+和Tb 3+进行了基于配位的发光研究，以开始探索新的配体结构的性质，并揭示了精胺支架具有更高的敏化效率以及结构类肽异构体之间的不同光谱特征。选定配体的溶液热力学性质显示，精胺和类肽类似物之间的配位性质不同，具有Eu