1-((5aR,6S,7S,7aR,10S,12aS,12bR,15R)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-8-oxo-5,5a,6,7,8,9,10,11,12,12a-decahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-2-yl)guanidine hydrochloride | 1443533-74-1

• 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: 1-((5aR,6S,7S,7aR,10S,12aS,12bR,15R)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-8-oxo-5,5a,6,7,8,9,10,11,12,12a-decahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-2-yl)guanidine hydrochloride
• 英文别名: 1-((5aR,6S,7S,7aR,10S,12aS,12bR,15R)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-8-oxo-5,5a,6,7,8,9,10,11,12,12adecahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-2-yl)guanidine；CYD-6-29；2-[(1R,9R,10S,11S,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-13-oxo-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-4-yl]guanidine;hydrochloride
• CAS: 1443533-74-1
• 化学式: C₂₂H₂₈N₄O₅S*ClH
• 分子量: 497.015
• InChiKey: PJKFGEVZGHVBKX-VESTXVLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.51
• 重原子数：
  33
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  193
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 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 1-((5aR,6S,7S,7aR,10S,12aS,12bR,15R)-6,7,15-trihydroxy-5,5-dimethyl-9-methylene-8-oxo-5,5a,6,7,8,9,10,11,12,12a-decahydro-4H-7,12b-(epoxymethano)-7a,10-methanocyclohepta[7,8]naphtho[1,2-d]thiazol-2-yl)guanidine hydrochloride
  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..