6-Formyl-8-methoxy-2,2-dimethyl-2H-<1>benzopyran | 71672-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-Formyl-8-methoxy-2,2-dimethyl-2H-<1>benzopyran
• 英文别名: 8-methoxy-2,2-dimethyl-2H-chromene-6-carbaldehyde；8-Methoxy-2,2-dimethyl-2H-1-benzopyran-6-carbaldehyde；8-methoxy-2,2-dimethylchromene-6-carbaldehyde
• CAS: 71672-22-5
• 化学式: C₁₃H₁₄O₃
• 分子量: 218.252
• InChiKey: IRMONAYMIVIKDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Formyl-8-methoxy-2,2-dimethyl-2H-<1>benzopyran 在 二异丁基氢化铝 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide
  参考文献：
  名称：

  Design and in Vitro Activities of N-Alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, Novel, Small-Molecule Hypoxia Inducible Factor-1 Pathway Inhibitors and Anticancer Agents

  摘要：

  The hypoxia inducible factor (HIF) pathway is an attractive target for cancer, as it controls tumor adaptation to growth under hypoxia and mediates chemotherapy and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide as a novel, small-molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 mu M in water; log P-7.4 = 3.7). Here we describe the synthesis of 12 N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental log P-7.4 values of 8 of the 12 new analogs ranged from 1.2-3.1. Aqueous solubilities of three analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide had an aqueous solubility of 80 mu M, e.g., a solubility improvement of similar to 9000-fold. The pharmacological optimization had limited impact on drug efficacy as the compounds retained IC50 values at or below 5 mu M in our HIF-dependent reporter assay.

  DOI：

  10.1021/jm300752n
• 作为产物：
  描述：

  4-(1,1-二甲基-2-丙炔氧基)-3-甲氧基苯甲醛 在 N,N-二乙基苯胺 作用下， 反应 1.5h， 以93%的产率得到6-Formyl-8-methoxy-2,2-dimethyl-2H-<1>benzopyran
  参考文献：
  名称：

  天然存在的烯丙基化和吡喃并邻苯二酚作为强效抗炎药的合成和药理特性

  摘要：

  摘要已开发出一种有效的方法来合成天然存在的烯丙基查耳酮。坎佐诺尔C（1），链球菌素（2），Crotaorixin（3），药物元素素（4），利加格查尔酮A（5）和Abyssinone D（6）以及吡喃丙酮副棕榈素C（7），蒽醌（8）和3- O。 -甲基杜鹃花A（9）。合成的关键步骤是克莱森-施密特缩合反应。随后，在脂多糖（LPS）诱导的RAW-264.7巨噬细胞中研究了它们的抗炎作用。在合成的查耳酮中，化合物5（IC 50 = 10.41μmol/ L），化合物6（IC 50 = 9.65μmol/ L）和化合物8（IC 50 = 15.34μmol/ L）表现出显着的活性，没有细胞毒性。化合物9（IC 50 = 4.5μmol/ L）表现出最大（83.6％）一氧化氮（NO）抑制作用，但显示出轻微的细胞毒性。

  DOI：

  10.1016/j.cclet.2016.01.043

文献信息

• Natural Product-like Combinatorial Libraries Based on Privileged Structures. 1. General Principles and Solid-Phase Synthesis of Benzopyrans
  作者：K. C. Nicolaou、J. A. Pfefferkorn、A. J. Roecker、G.-Q. Cao、S. Barluenga、H. J. Mitchell

  DOI：10.1021/ja002033k

  日期：2000.10.1

  report a novel strategy for the design and construction of natural and natural product-like libraries based on the principle of privileged structures, a term originally introduced to describe structural motifs capable of interacting with a variety of unrelated molecular targets. The identification of such privileged structures in natural products is discussed, and subsequently the 2,2-dimethylbenzopyran

  在此，我们报告了一种基于特权结构原理设计和构建天然和天然产物类库的新策略，该术语最初用于描述能够与各种不相关的分子靶标相互作用的结构基序。讨论了天然产物中此类特权结构的鉴定，随后选择 2,2-二甲基苯并吡喃部分作为通过该策略构建类天然产物库的初始模板。最初，采用独特的环加载策略开发了苯并吡喃基序的新型固相合成，该策略依赖于使用新的聚苯乙烯基溴化硒树脂。一旦确定了这些苯并吡喃的加载、加工和裂解，
• HYPOXIA INDUCIBLE FACTOR-1 PATHWAY INHIBITORS AND USES AS ANTICANCER AND IMAGING AGENTS
  申请人：EMORY UNIVERSITY

  公开号：US20130164218A1

  公开（公告）日：2013-06-27

  This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

  本公开涉及缺氧诱导因子-1通路抑制剂及其作为抗癌和成像剂的用途。在某些实施方式中，本公开考虑了在此披露的化合物和药物组成物。
• The synthesis and evaluation of new benzophenone derivatives as tubulin polymerization inhibitors
  作者：Shun Zhang、Baijiao An、Jun Yan、Ling Huang、Xingshu Li

  DOI：10.1039/c6ra16948a

  日期：——

  Inspired by the potent inhibition activity of phenstatin and millepachine against cancer cell growth, a series of new benzophenone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 10a exhibited 0.029–0.062 μM of IC50 for five human cancer cell lines, which is much better than that of the two leading compounds. Flow cytometric analysis showed that

  受苯达他汀和米拉帕星对癌细胞生长的有效抑制作用的启发，合成了一系列新的二苯甲酮衍生物并将其作为微管蛋白聚合抑制剂进行评估。其中，化合物10a对五种人类癌细胞系的IC 50值为0.029-0.062μM ，远优于两种主要化合物的IC 50。流式细胞仪分析表明10a诱导A549细胞G2 / M期阻滞和凋亡。细胞研究表明10a诱导的细胞凋亡与线粒体膜电位（MMP）的崩溃有关。总体而言，当前的研究表明，通过靶向微管蛋白，二苯甲酮衍生物是有前途的抗癌药。
• Chromenylmethyl pyrimidinediamines as antibacterial agents
  申请人：——

  公开号：US20030144246A1

  公开（公告）日：2003-07-31

  This invention is concerned with substituted chromene derivatives of the general formula (I) in which R 1 represents alkyl or cycloalkylalkyl, R 2 and R 3 each independently represent alkyl or cycloalkyl or taken together with the adjacent carbon atom represent a saturated 3- to 6-membered carbocyclic or heterocyclic ring, the alkyl, cycloalkyl, carbocyclic or heterocyclic ring being unsubstituted or substituted, and R 4 represents hydrogen, halogen cyano, alkyl, alkylthio, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkynyl, alkoxyalkyl, alkoxyalkynyl, trialkylsilyl, aryl or heteroaryl, and pharmaceutically acceptable acid addition salts of these compounds, their use as therapeutically active substances; medicaments based on these substances, optionally in combination with sulphonamides, and their production; the use of these substances as medicaments and for the production of antibacterially-active medicaments; as well as the manufacture of the compounds of formula (I) and their pharmaceutically acceptable acid addition salts and intermediates for their manufacture.

  这项发明涉及通式（I）的取代的咔咯喹啉衍生物，其中R1代表烷基或环烷基烷基，R2和R3分别独立地代表烷基或环烷基，或与相邻碳原子一起代表饱和的3-至6-成员碳环或杂环，所述烷基、环烷基、碳环或杂环可以是未取代的或取代的，R4代表氢、卤素、氰基、烷基、烷基硫基、烯基、炔基、羟基烷基、羟基炔基、烷氧基烷基、烷氧基炔基、三烷基硅基、芳基或杂环基，以及这些化合物的药学可接受的酸盐，它们作为治疗活性物质的用途；基于这些物质的药物，可选地与磺胺类药物结合使用；它们的生产；这些物质作为药物的用途以及用于生产抗菌活性药物；以及通式（I）的化合物及其药学可接受的酸盐和用于其制备的中间体的制造。
• Acylations of 2,2-Dimethyl-2<i>H</i>-chromenes
  作者：Seiji Yamaguchi、Satoru Yamamoto、Shoichi Abe、Yoshiyuki Kawase

  DOI：10.1246/bcsj.57.442

  日期：1984.2

  Orientation in acylation reactions of 2,2-dimethyl-2H-chromenes was studied. Five acetylchromenes were obtained with two methods and six formylchromenes were obtained with a third method. Demethylation of four acyl-methoxy-substituted chromenes gave the corresponding acylchromenols. 2,2-Dimethyl-2H-chromene-6-carboxylic acid (anofinic acid) was also obtained by oxidation of 6-formylchromene.

  研究了 2,2-二甲基-2H-苯酰化反应中的定向。通过两种方法得到了五个乙酰基苯并通过第三种方法得到了六个甲酰基苯并。四种酰基甲氧基取代色烯的脱甲基反应得到了相应的酰基色酚。通过 6-甲酰基色烯的氧化作用，还得到了 2,2-二甲基-2H-色烯-6-羧酸（anofinic acid）。