4-Chloro-2H-naphtho<1,2-b>pyran-2-one | 173210-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 4-Chloro-2H-naphtho<1,2-b>pyran-2-one
• 英文别名: 4-Chloro-2H-benzo[h]chromen-2-one；4-chlorobenzo[h]chromen-2-one
• CAS: 173210-20-3
• 化学式: C₁₃H₇ClO₂
• 分子量: 230.65
• InChiKey: OLRGVHDVBNCTHI-UHFFFAOYSA-N

物化性质

• 熔点：
  164-165 °C(Solv: ethanol (64-17-5))
• 沸点：
  421.8±33.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-苄基哌嗪 、 4-Chloro-2H-naphtho<1,2-b>pyran-2-one 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以52%的产率得到4-(4-benzylpiperazin-1-yl)-2H-benzo[h]chromen-2-one
  参考文献：
  名称：

  包含哌嗪部分的4-氨基-2H-苯并[h]铬-2-（one）（ABO）类似物的合成，生物学评估和分子对接。

  摘要：

  前列腺癌（PCa）是全球范围内与癌症相关的男性死亡的主要原因。为了开发潜在的抗前列腺癌药物，通过合理的药物修饰，设计并合成了22种4-氨基-2H-苯并[ h ]铬-2--2-酮类似物作为有效的雄激素受体（AR）拮抗剂，从而发现了一系列新的抗增殖化合物。类似物（3，4，5，7，8，10，11，12，16，18，21，23，和24）表现出对AR的强效拮抗作用（抑制> 50％），并且表现出有效的AR结合亲和力，并且对LNCaP细胞（富AR）比PC-3细胞（AR缺乏）表现出比非那雄胺更高的活性。此外，对接研究表明，最有效的拮抗剂23主要通过范德华力的相互作用与AR配体结合袋（LBP）位点结合。合理地探索和讨论了这些设计的4-氨基-2H-苯并[ h ]铬n-2-one类似物的构效关系（SAR）。总的来说，这项工作为与前列腺癌治疗有关的抗癌药开发提供了潜在的先导化合物，并朝着新型和改良的AR拮抗剂的发展迈出了一步。

  DOI：

  10.1016/j.bmc.2019.115081
• 作为产物：
  描述：

  2-乙酰基-1-萘酚 在 sodium hydride 、 三乙胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 7.75h， 生成 4-Chloro-2H-naphtho<1,2-b>pyran-2-one
  参考文献：
  名称：

  钯催化的功能化4-氯香豆素的化学选择性单芳基化和双芳基化，以三芳基铋为三重芳构化试剂

  摘要：

  在钯催化下，使用三芳基铋作为三重芳基化试剂，研究了不同取代的4-氯香豆素的交叉偶联反应。证明了4-氯香豆素的高反应性以化学选择性方式递送单芳基化和双芳基化产物。所采用的反应条件简单，稳定，并且在2-4小时的条件下，三芳基铋试剂的三重偶联反应性得到了良好的证明。在合成一些天然存在的新黄酮（3.27 – 3.30）中探索了该方法的实用性。另外，4-芳基香豆素3.1产物是制备（R）-托特罗定的有用前体。

  DOI：

  10.1016/j.tet.2014.07.059

文献信息

• Pyran derivatives
  作者：Mario Di Braccio、Giancarlo Grossi、Giorgio Roma、Cristina Marzano、Franca Baccichetti、Morena Simonato、Franco Bordin

  DOI：10.1016/s0014-827x(03)00160-5

  日期：2003.11

  The N-substituted tricyclic 2-aminochromone derivatives 1a, 2a, and 2b were obtained by treating the corresponding (methylthio) or (methylsulfinyl) derivatives 10, 11, or 12, respectively, with an excess of the proper amines. Compound 2c was synthesized through the reaction of 2-naphthol with the ethyl N,N-diphenylmalonamate/POCl(3) reagent 14. The N-substituted 4-aminocoumarin bicyclic and tricyclic derivatives 5-8 were prepared by treating the corresponding chloro derivatives with the excess suitable amines. Compounds 1, 2, 5-8 were tested in vitro for their antiproliferative activity (DNA synthesis inhibition in Ehrlich cells) and cytotoxicity (MTT test in HeLa cells). The inhibitory properties of three selected compounds (5c, 5e, 7c) on protein and RNA syntheses in Ehrlich cells were also evaluated. Among the 27 compounds tested, 10 4-aminocoumarin derivatives (5-8) and two 2-aminochromone derivatives (1a and 2a) showed an appreciable antiproliferative activity (IC(50) range: 1.74-13.8 microM), whereas only four compounds 5-8 exhibited a comparable cytotoxic activity (IC(50) range: 4.95-12.9 microM).
• Di Braccio; Roma; Leoncini, Il Farmaco, 1995, vol. 50, # 10, p. 703 - 711
  作者：Di Braccio、Roma、Leoncini、Poggi

  DOI：——

  日期：——
• Antitumor agents 278. 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs as potent in vitro anti-cancer agents
  作者：Yizhou Dong、Kyoko Nakagawa-Goto、Chin-Yu Lai、Susan L. Morris-Natschke、Kenneth F. Bastow、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2010.05.079

  日期：2010.7

  4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs were designed, synthesized, and evaluated for cytotoxic activity. Among all 4-substituted ABO analogs, cyclohexyl (12), N-methoxy-N-methylacetamide (14), and various aromatic derivatives (15-25 and 27) exhibited promising cell growth inhibitory activity with ED(50) values of 0.01-5.8 mu M against all tested tumor cell lines. The 4'-methoxyphenyl derivative (18) and 3'-methylphenyl derivative (24) showed the most potent antitumor activity against a broad range of cancer cell lines with ED(50) values of 0.01-76 mu M. Preliminary SAR results indicated that substitutions on nitrogen are critical to the antitumor potency. (C) 2010 Elsevier Ltd. All rights reserved.
• Pyran derivatives XX. 2-Aminochromone benzo-fused derivatives with antiproliferative properties
  作者：Giorgio Roma、Mario Di Braccio、Giancarlo Grossi、Cristina Marzano、Morena Simonato、Franco Bordin

  DOI：10.1016/s0014-827x(98)00055-x

  日期：1998.7

  The N-substituted 2-aminochromones 1 and their benzo-fused derivatives 2-4 described herein were mostly prepared by treating the corresponding (methylthio) derivatives 10-13 with an excess of the proper amines. Only the morpholino derivatives 3d and 4c were obtained from the reaction of the ethyl 3-morpholino-3-oxopropanoate/POCl3 reagent with 1-naphthol or 1-methyl-2-naphthol, respectively. The amino derivatives 1-4, as well as their methylthio analogues 10-13, were tested in vitro for their inhibitory activity on the infectivity of T2 bacteriophage, on the macromolecular synthesis in Ehrlich cells and on the clonal growth capacity of HeLa cells. Several of the angular or linear aminonaphthopyranones 2 and 3 or 4, respectively, and the (methylthio) derivatives 10, 11 and 13 induced a significant inhibition of DNA synthesis, but usually a clearly lower inhibition of clonal growth. Only the Linear 2-amino-10-methyl-4H-naphtho [2,3-b]pyran-4-ones 4a and 4b significantly inhibited the clonal growth in HeLa cells and T2 bacteriophage infectivity, respectively. (C) 1998 Elsevier Science S.A. All rights reserved.
• Antitumor Agents. 289. Design, Synthesis, and Anti-Breast Cancer Activity in Vivo of 4-Amino-2<i>H</i>-benzo[<i>h</i>]chromen-2-one and 4-Amino-7,8,9,10-tetrahydro-2<i>H</i>-benzo[<i>h</i>]chromen-2-one Analogues with Improved Water Solubility
  作者：Yizhou Dong、Kyoko Nakagawa-Goto、Chin-Yu Lai、Susan L. Morris-Natschke、Kenneth F. Bastow、Yoon Kim、Eva Y.-H. P. Lee、Kuo-Hsiung Lee

  DOI：10.1021/np2007878

  日期：2012.3.23

  Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues, with IC50 values of 0.038-0.085 mu M in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4[(4'-methoxyphenyl)amino]-2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells, as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and a mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate.