(6S,7S,7aR,10R,12bR,15R)-2-(cyclohexylamino)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-5,5a,6,7,10,11,12,12a-octahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-8(9R)-one | 1443533-69-4

• 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: (6S,7S,7aR,10R,12bR,15R)-2-(cyclohexylamino)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-5,5a,6,7,10,11,12,12a-octahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-8(9R)-one
• 英文别名: (6S,7S,7aR,10R,12bR,15R)-2-(cyclohexylamino)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-5,5a,6,7,10,11,12,12a-octahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta-[7,8]naphtho[1,2-d]thiazol-8(9H)-one；CYD-6-17-2；CYD0617；(1R,9R,10S,11S,12R,15S,18S,21R)-4-(cyclohexylamino)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one
• CAS: 1443533-69-4
• 化学式: C₂₇H₃₆N₂O₅S
• 分子量: 500.659
• InChiKey: SAPHFMWLARVIJH-SXWPZXSPSA-N

物化性质

• 沸点：
  697.4±65.0 °C(predicted)
• 密度：
  1.41±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6S,7S,7aR,10R,12bR,15R)-2-(cyclohexylamino)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-5,5a,6,7,10,11,12,12a-octahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-8(9R)-one 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 反应 8.0h， 以82%的产率得到(6S,6aR,6a1R,9aR,10S,12bR)-2-(cyclohexylamino)-6-hydroxy-5,5,8,8-tetramethyl-15-methylene-4,5,5a,6,9a,10,12,12a-octahydro-11H-6a,12b-(epoxymethano)-6a1,10-ethano[1,3]dioxino[4’,5’,6’:8,9]phenanthro[4,3-d]thiazol-16-one
  参考文献：
  名称：

  区域和立体定向合成的Oridonin D环叠氮iri类似物通过介导的不可逆共价战斗部治疗三阴性乳腺癌。

  摘要：

  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。

  DOI：

  10.1021/acs.jmedchem.7b01514
• 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 pyridinium hydrobromide perbromide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 7.0h， 生成 (6S,7S,7aR,10R,12bR,15R)-2-(cyclohexylamino)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-5,5a,6,7,10,11,12,12a-octahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-8(9R)-one
  参考文献：
  名称：

  [EN] ORIDONIN ANALOGS, COMPOSITIONS, AND METHODS RELATED THERETO
  [FR] ANALOGUES D'ORIDONINE, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS

  摘要：

  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。

  公开号：

  WO2014165841A1

文献信息

• Novel Nitrogen-Enriched Oridonin Analogues with Thiazole-Fused A-Ring: Protecting Group-Free Synthesis, Enhanced Anticancer Profile, and Improved Aqueous Solubility
  作者：Chunyong Ding、Yusong Zhang、Haijun Chen、Zhengduo Yang、Christopher Wild、Lili Chu、Huiling Liu、Qiang Shen、Jia Zhou

  DOI：10.1021/jm400367n

  日期：2013.6.27

  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..
• 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.