CYD-5-29 | 133082-35-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: CYD-5-29
• 英文别名: (1S,2S,5S,8R,9R,13R,14S,15R)-14-hydroxy-11,11,16,16-tetramethyl-6-methylidene-10,12,21-trioxahexacyclo[11.6.2.01,15.02,8.05,9.08,13]henicosane-7,19-dione
• CAS: 133082-35-6
• 化学式: C₂₃H₃₀O₆
• 分子量: 402.488
• InChiKey: BVUJDTDPXPIPJQ-XVJLLRTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  29
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  CYD-5-29 在 pyridinium hydrobromide perbromide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以40%的产率得到CYD-5-43
  参考文献：
  名称：

  Novel Nitrogen-Enriched Oridonin Analogues with Thiazole-Fused A-Ring: Protecting Group-Free Synthesis, Enhanced Anticancer Profile, and Improved Aqueous Solubility

  摘要：

  Oridonin (1), a complex ent-kaurane diterpenoid isolated from the traditional Chinese herb Isodon rubescens, has demonstrated great potential in the treatment of various human cancers due to its unique and safe anticancer pharmacological profile. Nevertheless, the clinical development of oridonin for cancer therapy has been hampered by its relatively moderate potency, limited aqueous solubility, and poor bioavailability. Herein, we report the concise synthesis of a series of novel nitrogen. enriched oridonin derivatives with thiazole-fused A-ring through an efficient protecting group-free synthetic strategy. Most of them, including compounds 7-11, 13, and 14, exhibited potent antiproliferative effects against breast, pancreatic, and prostate cancer cells with low micromolar to submicromolar IC50 values as well as markedly enhanced aqueous solubility. These new analogues obtained by rationally modifying the natural product have been demonstrated not only to significantly induce the apoptosis and suppress growth of triple-negative MDA-MB-231 breast cancer both in vitro:and in vivo but also effective against drug resistant ER positive MCF-7 clones..

  DOI：

  10.1021/jm400367n
• 作为产物：
  描述：

  (4aR,5S,6S,6aR,9S,11aS,11bS,14R)-5,6,14-trihydroxy-4,4-dimethyl-8-methylenedecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalene-1,7(8H)-dione 在 对甲苯磺酸 、 2,2-二甲氧基丙烷 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以95%的产率得到CYD-5-29
  参考文献：
  名称：

  基于 Oridonin 环 A 的烯酮功能的多样化构建：通过诱导细胞凋亡鉴定对高度侵袭性乳腺癌有效的新型二烯酮类似物

  摘要：

  冬凌草素 ( 1) 由于其独特且安全的抗癌药理特性，近年来引起了相当大的关注。然而，它对高度侵袭性癌症（包括三阴性和耐药性乳腺癌细胞）表现出中等至较差的效果。在此，我们报告了基于此类具有密集功能和立体化学丰富框架的天然支架，合理设计和合成了具有不同安装在 A 环中的额外 α,β-不饱和酮系统的新型二烯酮衍生物。已经建立了有效和区域选择性的烯酮构建策略。同时，发现了一种独特的 3,7-重排反应，以提供前所未有的二烯酮支架。耐人寻味的是，1 .

  DOI：

  10.1021/jm401248x

文献信息

• [EN] ORIDONIN ANALOGS, COMPOSITIONS, AND METHODS RELATED THERETO<br/>[FR] ANALOGUES D'ORIDONINE, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV TEXAS

  公开号：WO2014165841A1

  公开（公告）日：2014-10-09

  Certain embodiments are directed to oridonin analogs or derivatives. In aspects, the derivatives are used as anticancer or anti-inflammatory agents.

  某些实施例涉及苦参酮类似物或衍生物。在某些方面，这些衍生物被用作抗癌或抗炎药物。
• Regio- and Stereospecific Synthesis of Oridonin D-Ring Aziridinated Analogues for the Treatment of Triple-Negative Breast Cancer via Mediated Irreversible Covalent Warheads
  作者：Ye Ding、Dengfeng Li、Chunyong Ding、Pingyuan Wang、Zhiqing Liu、Eric A. Wold、Na Ye、Haiying Chen、Mark A. White、Qiang Shen、Jia Zhou

  DOI：10.1021/acs.jmedchem.7b01514

  日期：2018.4.12

  Herein, for the first time, we report the excessive reactivity of this covalent warhead and mediation of the covalent binding capability through a Rh2(esp)2-catalyzed mild and concise regio- and stereospecific aziridination approach. Importantly, aziridonin 44 (YD0514), with a more-druglike irreversible covalent warhead, has been identified to significantly induce apoptosis and inhibit colony formation

  由于对共价药物候选物的结构-活性关系（SAR）和结构-反应性关系（SRR）进行了全面优化，近年来，共价药物的发现已经复苏。天然产物冬凌草甲素通过其在D环上的共价烯酮弹头保持令人印象深刻的药理作用，并吸引了大量的SAR研究，以表征其在开发用于治疗各种人类癌症和炎症的新分子实体方面的潜力。在本文中，我们首次报道了这种共价战斗部的过度反应性，并通过Rh 2（esp）2催化的温和而简洁的区域和立体定向叠氮化方法介导了共价结合能力。重要的是，阿奇多宁44（YD0514）具有更药性的不可逆共价战斗部，已被证实可显着诱导凋亡并抑制针对三阴性乳腺癌的集落形成，在体内外均具有增强的抗肿瘤作用，同时对正常人乳腺上皮细胞显示出较低的毒性与冬凌草甲素相比。
• ORIDONIN ANALOGS, COMPOSITIONS, AND METHODS RELATED THERETO
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US20170313716A1

  公开（公告）日：2017-11-02

  Certain embodiments are directed to oridonin analogs or derivatives. In certain aspects, the derivatives are used as anticancer or anti-inflammatory agents.
• US9725460B2
  申请人：——

  公开号：US9725460B2

  公开（公告）日：2017-08-08