2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde | 908860-66-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde
• 英文别名: 5-Formyl-indan-1-one 1,2-ethanediol ketal；spiro[1,3-dioxolane-2,1'-2,3-dihydroindene]-5'-carbaldehyde
• CAS: 908860-66-2
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: XWXCHFBHCGXDJI-UHFFFAOYSA-N

物化性质

• 沸点：
  349.8±42.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide sodium tetrahydroborate 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， 反应 6.5h， 生成 3-(5-(3-(4-Chlorophenoxy)prop-1-ynyl)thiophen-3-yl)-6-((4-methylpiperazin-1-yl)methyl)-1,4-dihydroindeno[1,2-c]pyrazole
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  5-溴茚酮 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 苯 为溶剂， 反应 48.92h， 生成 2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde
  参考文献：
  名称：

  小分子CD4-模拟物：HIV-1进入抑制的基于结构的优化。

  摘要：

  基于计算，热力学和晶体学数据，已对人免疫缺陷病毒（HIV）包膜糖蛋白gp120的Phe43腔的一系列小分子配体进行了优化。重要的是，生物评价，发现该小分子模拟物的CD4（4 - 7）抑制HIV-1进入与两个显著更高的效力和中和广度比以前的同源物的靶细胞，同时保持靶病毒高选择性。通过热力学和晶体学研究表征了它们的结合模式。

  DOI：

  10.1021/acsmedchemlett.5b00471

文献信息

• [EN] INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE PÉNÉTRATION DU VIH-1 ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV PENNSYLVANIA

  公开号：WO2016025681A1

  公开（公告）日：2016-02-18

  The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.

  该披露提供了一种使原发性HIV-1，包括传播/创始病毒，对单克隆抗体中和敏感化的组合物和方法，例如那些针对CD4诱导（CD4i）表位和V3区域的抗体。在某些实施例中，该披露涉及将小分子用作微生物灭活剂，直接抑制HIV-1感染并使原发性HIV-1对易产生的抗体中和敏感化的用途。
• Cross-Selective Aza-Pinacol Coupling via Atom Transfer Catalysis
  作者：Sean M. Rafferty、Joy E. Rutherford、Lumin Zhang、Lu Wang、David A. Nagib

  DOI：10.1021/jacs.1c00886

  日期：2021.4.21

  homodimerization by a classical reductive approach. In this first example of reductive, ketyl coupling by atom transfer catalysis, Zn serves as a terminal reductant to facilitate Mn catalyst turnover. This new strategy also enables ketyl radical couplings to alkenes, alkynes, aldehydes, propellanes, and chiral imines.

  已经开发了醛和亚胺的交叉选择性氮杂频哪醇偶联以提供有价值的β-氨基醇。这种策略能够在更容易还原的亚胺和其他官能团的存在下，将脂肪醛化学选择性地转化为酮基自由基。通过 AcI 进行羰基特异性活化后，光引发的 Mn 催化剂通过原子转移机制选择性地还原生成的 α-碘氧化物。随后的酮基自由基选择性地与亚胺偶联，从而阻止了通过经典还原方法进行的均二聚化。在通过原子转移催化还原酮基偶联的第一个例子中，Zn 作为末端还原剂以促进 Mn 催化剂的周转。这种新策略还可以使酮基自由基偶联到烯烃、炔烃、醛、螺旋桨和手性亚胺上。
• Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors
  作者：Jürgen Dinges、Irini Akritopoulou-Zanze、Lee D. Arnold、Teresa Barlozzari、Peter F. Bousquet、George A. Cunha、Anna M. Ericsson、Nobuhiko Iwasaki、Michael R. Michaelides、Nobuo Ogawa、Kathleen M. Phelan、Paul Rafferty、Thomas J. Sowin、Kent D. Stewart、Ryukou Tokuyama、Zhiren Xia、Henry Q. Zhang

  DOI：10.1016/j.bmcl.2006.05.052

  日期：2006.8

  A series of 1,4-dihydroindeno[1,2-c]pyrazoles was prepared and evaluated for their enzymatic inhibition of KDR kinase. Computer modeling studies revealed the importance of attaching a basic side chain in predicting The binding mode of those compounds. Further investigation of structure-activity relationships led to 19, a lead compound with an acceptable selectivity profile, activity in whole cells, and good oral efficacy in an estradiol-induced murine uterine edema model of VEGF activity. (c) 2006 Elsevier Ltd. All rights reserved.
• INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF
  申请人：The Trustees of The University of Pennsylvania

  公开号：US20170233335A1

  公开（公告）日：2017-08-17

  The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.
• US9975848B2
  申请人：——

  公开号：US9975848B2

  公开（公告）日：2018-05-22