(1S,6R)-3,5-二溴-1,6-二羟基-4-甲氧基-2,4-环己二烯-1-乙腈 | 28656-91-9

• 物质功能分类: 生物 - 生化试剂盒
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1S,6R)-3,5-二溴-1,6-二羟基-4-甲氧基-2,4-环己二烯-1-乙腈
• 英文名称: Aeroplysinin I
• 英文别名: (+)-aeroplysinin-1；Aeroplysinin-1；aeroplysinin 1；2-[(1S,6R)-3,5-dibromo-1,6-dihydroxy-4-methoxycyclohexa-2,4-dien-1-yl]acetonitrile
• CAS: 28656-91-9
• 化学式: C₉H₉Br₂NO₃
• 分子量: 338.983
• InChiKey: BGYNLOSBKBOJJD-IUCAKERBSA-N

物化性质

• 沸点：
  479.6±45.0 °C(Predicted)
• 密度：
  2.01±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于甲醇：

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  73.5
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

Aeroplysinin 1 ((+)-Aeroplysinin-1) 是从海洋海绵中分离出的次生代谢产物，对革兰氏阳性细菌显示出有效的抗生素作用，并具有针对 HIV-1 的抗病毒活性 (IC50=14.6 μM)。此外，它还表现出抗炎、抗血管生成和抗肿瘤活性。Aeroplysinin 1 可诱导内皮细胞凋亡。

靶点

细菌	HIV-1	14.6 μM (IC50)
内皮细胞凋亡

体外研究

Aeroplysinin 1 对多种肿瘤细胞（HT-1080、HTC-116、HeLa、THP-1、NOMO-1 和 HL-60 细胞）表现出抗增殖作用，IC50 值范围从 2.3 到 17 μM。此外，它还具有抑制 HIV-1 的抗病毒活性，并能通过抑制其逆转录酶的活性来发挥这一作用。

Aeroplysinin 1 对以下几种生物表现出抑制活性：P. phosphoreum、C. wailesii、P. minimum 和 HIV，IC50 值分别为 3.5、5.6、7.0 和 14.6 μM。Aeroplysinin 1 对人类内皮细胞（EVLC-2、HMEC、RF-24 和 HUVEC 细胞）的抑制作用，IC50 值范围从 2.6 到 4.7 μM。

此外，(+)Aeroplysinin-1 (0.25-0.5 μM) 可以阻断 EGF 依赖性乳腺癌细胞（MCF-7 和 ZR-75-1）的增殖，并抑制配体诱导的 EGFR 内吞作用。

反应信息

• 作为反应物：
  描述：

  (1S,6R)-3,5-二溴-1,6-二羟基-4-甲氧基-2,4-环己二烯-1-乙腈 在 咪唑 、 marine sponge Aplysina aerophoba 作用下， 以 乙醇 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  Wound Activation of Protoxins in Marine Sponge Aplysina aerophoba

  摘要：

  The marine sponge Aplysina aerophoba accumulates brominated isoxazoline alkaloids, which include aerophobin-2, aplysinamisin-1, and isofistularin-3 as major constituents. Following disruption of compartmentalization, the isoxazoline alkaloids are enzymatically converted to aeroplysinin-1, which in rum gives rise to a dienone. The described bioconversions were demonstrated for the first time in vitro using an enzyme preparation from A. aerophoba. Cell-free extracts of other Aplysina species were capable of performing the same bioconversions, whereas enzyme extracts of sponges from other orders, which lack isoxazoline alkaloids, were inactive with regard to the reactions analyzed. These findings suggest that the enzyme activities studied are linked to the accumulation of suitable substrates and hence represent a specific biochemical property of sponges from the genus Aplysina. Time-course experiments with A. aerophoba, performed in situ, demonstrated that wound-induced bioconversions of isoxazoline alkaloids proceeded rapidly. Within 40 sec after mechanical damage of a tube of A. aerophoba, both aerophobin-2 and aplysinamisin-1 were completely converted to the dienone. The wound activation of protoxins results in a pronounced increase of the fish deterrent activity of A. aerophoba as shown in bioassays employing the common Caribbean wrasse Thalassoma bifasciatum.

  DOI：

  10.1023/b:joec.0000006475.10310.3a
• 作为产物：
  描述：

  (5S*,6R*)-methyl 7,9-dibromo-8-methoxy-6-oxo-1-oxa-2-azaspiro<4.5>deca-2,7,9-triene-3-carboxylate 在 sodium hydroxide 作用下， 以94%的产率得到(1S,6R)-3,5-二溴-1,6-二羟基-4-甲氧基-2,4-环己二烯-1-乙腈
  参考文献：
  名称：

  Asymmetric synthesis of aerothionin, a marine dimeric spiroisoxazoline natural product, employing optically active spiroisoxazoline derivative

  摘要：

  Successful first synthesis of optically pure (+)- and (-)-aerothionins (1) from the racemic spiroisoxazoline derivative 8 has been accomplished. The absolute configuration of natural (+)-1 was determined by comparison of (+)- and (-)-8 with related derivatives. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.11.097

文献信息

• [EN] CRYSTALLINE FORMS OF C21H22CI2N4O2<br/>[FR] FORMES CRISTALLINES DE C21H22CI2N4O2
  申请人：BIOMED VALLEY DISCOVERIES INC

  公开号：WO2016123574A1

  公开（公告）日：2016-08-04

  The present invention provides crystalline forms of a compound of formula (I). Also provided are pharmaceutical compositions that include the provided crystalline forms and methods of using the provided crystalline forms and pharmaceutical compositions for the treatment of cancer. It has been discovered that crystalline forms of 4-(5-Chloro-2- isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2- hydroxyethyl]amide can be prepared which exhibit improved properties, e.g. surprisingly improved stability and improved solubility characteristics. Thus, the present invention provides crystalline 4-(5-Chloro-2- isopropylaminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2- hydroxyethyljamide.

  本发明提供了式（I）化合物的晶体形式。还提供了包括所提供的晶体形式的药物组合物以及使用所提供的晶体形式和药物组合物治疗癌症的方法。发现可以制备4-（5-氯-2-异丙基氨基吡啶-4-基）-1H-吡咯-2-羧酸[1-（3-氯苯基）-2-羟乙基]酰胺的晶体形式，其具有改进的特性，例如惊人的稳定性和改进的溶解性特性。因此，本发明提供了晶体4-（5-氯-2-异丙基氨基吡啶-4-基）-1H-吡咯-2-羧酸[1-（3-氯苯基）-2-羟乙基]酰胺。
• [EN] CRYSTALLINE C21H22C12N4O2 MALONATE<br/>[FR] MALONATE CRISTALLIN C21H22C12N4O2
  申请人：BIOMED VALLEY DISCOVERIES INC

  公开号：WO2016123581A1

  公开（公告）日：2016-08-04

  The present invention provides a malonate salt of a compound of formula (I), which is a crystalline salt. Also provided are pharmaceutical compositions that include the provided malonate salt and methods of using the provided crystalline forms and pharmaceutical compositions for the treatment of cancer.

  本发明提供了式(I)化合物的丙二酸盐，其为结晶盐。还提供了包括所提供的丙二酸盐的药物组合物以及使用所提供的结晶形式和药物组合物治疗癌症的方法。
• Dibromotyrosine derivatives from the ethanol extract of the marine sponge Aplysina sp.: structures, transformations, and origin
  作者：E. A. Santalova、V. A. Denisenko、V. P. Glazunov、A. I. Kalinovskii、S. D. Anastyuk、V. A. Stonik

  DOI：10.1007/s11172-011-0088-9

  日期：2011.3

  Twenty nine 3,5-dibromotyrosine derivatives were isolated from the ethanol extract of the marine sponge Aplysina sp. (South China Sea) including the earlier unknown compounds, in particular, p-hydroxycyclohexadienone and p-hydroxycyclohexenone ketals. The isolated enones, dienones, and ketals can be transformation products of aeroplysinin-1 in the course of its reactions with water and alcohols.

  从海洋海绵（中国南海）的乙醇提取物中分离出29种3,5-二溴酪氨酸衍生物，包括之前未知的化合物，特别是对羟基环己二烯酮和对羟基环己烯酮缩酮。分离出的烯酮、二烯酮和缩酮可能是气生菌素-1与水和醇反应过程中的转化产物。
• An Aeroplysinin-1 Specific Nitrile Hydratase Isolated from the Marine Sponge Aplysina cavernicola
  作者：Bartosz Lipowicz、Nils Hanekop、Lutz Schmitt、Peter Proksch

  DOI：10.3390/md11083046

  日期：——

  characterized from the Mediterranean sponge Aplysina cavernicola; although it is currently not known whether the enzyme is of sponge origin or produced by its symbiotic microorganisms. The formation of aeroplysinin-1 and of the corresponding dienone amide is part of the chemical defence system of A. cavernicola. The latter two compounds that show strong antibiotic activity originate from brominated isoxazoline

  从地中海海绵海兔中分离、部分纯化并表征了一种腈水合酶 (NHase)，它特异性接受腈 aeroplysinin-1 (1) 作为底物并将其转化为二烯酮酰胺 verongiaquinol (7)；尽管目前尚不清楚该酶是源自海绵还是由其共生微生物产生。aeroplysinin-1 和相应的二烯酮酰胺的形成是 A.cabernicola 化学防御系统的一部分。后两种显示出强抗生素活性的化合物源自溴化异恶唑啉生物碱，被认为可以保护海绵免受细菌病原体的入侵。海绵被证明含有至少两个 NHase，因为从非变性 Blue Native 凝胶中切下的两个蛋白质条带显示出腈水合酶活性，这在对照样品中没有观察到。尽管钴和镍离子也能够恢复腈水合酶的活性，但这些酶被证明是依赖于锰的。发现所研究酶的最适温度和 pH 值为 41 °C，pH 值为 7.8。这些酶对生理底物 aeroplysinin-1 (1) 显示出高
• CRYSTALLINE FORMS OF C21H22Cl2N4O2
  申请人：BIOMED VALLEY DISCOVERIES, INC.

  公开号：US20170320851A1

  公开（公告）日：2017-11-09

  The present invention provides crystalline forms of a compound of formula (I): Also provided are pharmaceutical compositions that include the provided crystalline forms and methods of using the provided crystalline forms and pharmaceutical compositions for the treatment of cancer.

  本发明提供了公式（I）化合物的晶体形式。还提供包含所提供晶体形式的药物组合物以及使用所提供的晶体形式和药物组合物治疗癌症的方法。