10-bromomethyl-12-oxocalanolide A | 1017281-53-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 10-bromomethyl-12-oxocalanolide A
• 英文别名: 6,6,10-trimethyl-4-n-propyl-10-bromomethyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b'']tripyranyl-2,12-dione；16-(Bromomethyl)-10,10-dimethyl-6-propyl-3,9,15-trioxatetracyclo[12.4.0.02,7.08,13]octadeca-1(14),2(7),5,8(13),11-pentaene-4,18-dione
• CAS: 1017281-53-6
• 化学式: C₂₁H₂₁BrO₅
• 分子量: 433.299
• InChiKey: DSWAHIVYQGQNPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  哌啶 、 10-bromomethyl-12-oxocalanolide A 以 四氢呋喃 为溶剂， 以69%的产率得到11-demethyl-12-oxo-10-piperidinemethylcalanolide A
  参考文献：
  名称：

  Highly Suppressing Wild-Type HIV-1 and Y181C Mutant HIV-1 Strains by 10-Chloromethyl-11-demethyl-12-oxo-calanolide A with Druggable Profile

  摘要：

  We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC50 = 7.4 nM, St = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC50 = 7.4 nM and EC50 = 0.46 nM, respectively.

  DOI：

  10.1021/jm901653e
• 作为产物：
  描述：

  1,1-二乙氧基-3-甲基-2-丁烯 、 8-(bromomethyl)-5-hydroxy-4-propyl-8,9-dihydro-2H,10H-pyrano[2,3-f]chromene-2,10-dione 在 吡啶 作用下， 以 甲苯 为溶剂， 以88%的产率得到10-bromomethyl-12-oxocalanolide A
  参考文献：
  名称：

  Chemical Library and Structure–Activity Relationships of 11-Demethyl-12-oxo Calanolide A Analogues as Anti-HIV-1 Agents

  摘要：

  (+)-Calanolide A (1) 作为一种天然产物，先前被发现是HIV-1逆转录酶的抑制剂。在我们对其模板的进一步研究中，外消旋的11-去甲基-12-酮基calanolide A (15) 被发现。与(+)-calanolide A相比，它在C-11和C-12位上少两个手性碳中心，但其对HIV-1的抑制活性相当，并且具有更好的治疗指数（EC(50) = 0.11 μM，TI = 818）。随后，基于其结构核心设计并合成了一个化合物库，并在本文中引入了九个多样性点。体外评估抗HIV-1活性得出了它们的结构-活性关系（SARs）。发现了一个新的化合物（10-溴甲基-11-去甲基-12-酮基calanolide A，123），其对HIV-1的抑制效力和治疗指数（EC(50) = 2.85 nM，TI > 10,526）显著高于该类化合物。这一发现提供了非常重要的线索，即对C环的C-10位进行修饰，可能会得到对HIV-1活性更好的药物候选物。

  DOI：

  10.1021/jm701405p

文献信息

• TETRACYCLIC DIPYRANO-COUMARIN COMPOUNDS WITH ANTI-HIV AND ANTI-MYCOBACTERIUM TUBERCULOSIS ACTIVITIES
  申请人：Liu Gang

  公开号：US20100324067A1

  公开（公告）日：2010-12-23

  The present invention relates to tetracyclodipyrano-coumarin compounds of general formula (I), wherein the substituents are defined herein. These compounds exihibit dual biological activities of anti human immunodeficiency virus type 1 (HIV-1) infection and anti- Mycobacterium Tuberculosis (TB) infection.

  本发明涉及通式（I）的四环二吡喃香豆素类化合物，其中取代基在此定义。这些化合物表现出抗人类免疫缺陷病毒类型1（HIV-1）感染和抗结核分枝杆菌（TB）感染的双重生物活性。
• A new method for the synthesis of N-substituted pyrroles
  作者：Hai Xue、Tao Ma、Lin Wang、Gang Liu

  DOI：10.1016/j.cclet.2010.04.030

  日期：2010.11

  Abstract An unexpected reaction of 10-bromomethyl-12-oxocalanolide A (2) with primary amine was demonstrated and studied. Consequentially, a new method for the preparation of N-substituted pyrroles starting from γ-halo-α,β-unsaturated ketone was presented.

  摘要证明并研究了10-溴甲基-12-草酰乙醇胺A（2）与伯胺的意外反应。因此，提出了一种从γ-卤代-α，β-不饱和酮制备N-取代吡咯的新方法。
• TETRACYCLODIPYRANYL COUMARINS AND THE ANTI-HIV AND ANTI-TUBERCULOSIS USES THEREOF
  申请人：Institute of Mataria Medica, Chinese Academy of Medical Sciences

  公开号：EP2216335B1

  公开（公告）日：2014-03-12
• Chemical Library and Structure–Activity Relationships of 11-Demethyl-12-oxo Calanolide A Analogues as Anti-HIV-1 Agents
  作者：Tao Ma、Li Liu、Hai Xue、Li Li、Chunyan Han、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm701405p

  日期：2008.3.13

  (+)-Calanolide A (1) as a natural product was previously found as an inhibitor of HIV-1 reverse tratiscriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A (15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC(50) = 0.11 mu M, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC(50) = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.

  (+)-Calanolide A (1) 作为一种天然产物，先前被发现是HIV-1逆转录酶的抑制剂。在我们对其模板的进一步研究中，外消旋的11-去甲基-12-酮基calanolide A (15) 被发现。与(+)-calanolide A相比，它在C-11和C-12位上少两个手性碳中心，但其对HIV-1的抑制活性相当，并且具有更好的治疗指数（EC(50) = 0.11 μM，TI = 818）。随后，基于其结构核心设计并合成了一个化合物库，并在本文中引入了九个多样性点。体外评估抗HIV-1活性得出了它们的结构-活性关系（SARs）。发现了一个新的化合物（10-溴甲基-11-去甲基-12-酮基calanolide A，123），其对HIV-1的抑制效力和治疗指数（EC(50) = 2.85 nM，TI > 10,526）显著高于该类化合物。这一发现提供了非常重要的线索，即对C环的C-10位进行修饰，可能会得到对HIV-1活性更好的药物候选物。
• Highly Suppressing Wild-Type HIV-1 and Y181C Mutant HIV-1 Strains by 10-Chloromethyl-11-demethyl-12-oxo-calanolide A with Druggable Profile
  作者：Hai Xue、Xiaofan Lu、Purong Zheng、Li Liu、Chunyan Han、Jinping Hu、Zijie Liu、Tao Ma、Yan Li、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm901653e

  日期：2010.2.11

  We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC50 = 7.4 nM, St = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC50 = 7.4 nM and EC50 = 0.46 nM, respectively.