(1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1-hyd roxy-9,10-[(1S)-2-propenylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate | 512186-56-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1-hyd roxy-9,10-[(1S)-2-propenylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate
• 英文别名: [(2R,4S,6S,7R,10R,13S,14R,15S,16S,18S)-13-acetyloxy-4-ethenyl-16-hydroxy-18-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pyridin-2-ylpropanoyl]oxy-7,19,20,20-tetramethyl-3,5,11-trioxapentacyclo[14.3.1.02,6.07,14.010,13]icos-1(19)-en-15-yl] benzoate
• CAS: 512186-56-0
• 化学式: C₄₅H₅₆N₂O₁₃
• 分子量: 832.945
• InChiKey: BJQLKVHHTWQUDM-UOWCRDOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  60
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  198
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1-hyd roxy-9,10-[(1S)-2-propenylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate 在 四氧化锇 、 N-甲基吗啉氧化物 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 氯仿 、 水 、 丙酮 为溶剂， 反应 1.0h， 生成 (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2,3-dihydroxypropylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate
  参考文献：
  名称：

  New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals. Part 4

  摘要：

  It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1. generated by human liver microsomes as 20a, a hydroxylated compound at the pyridine ring of 3. To improve the metabolic stability of 3, we designed and synthesized new taxane analogues based on the structure of M-1. and obtained some compounds that maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00454-1
• 作为产物：
  描述：

  (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1,9,10,13-tetrahydroxytax-11-ene 在 camphor-10-sulfonic acid 、 四丁基氟化铵 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1-hyd roxy-9,10-[(1S)-2-propenylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate
  参考文献：
  名称：

  New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 3

  摘要：

  We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00891-0

文献信息

• TAXANE COMPOUND WITH AZETIDINE RING STRUCTURE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1942109A1

  公开（公告）日：2008-07-09

  A compound represented by the general formula (1) [X1 and X2 represent hydrogen atom, a halogen atom, hydroxyl group and the like, R1 represents a phenyl group, R2 represents an alkyl group, an alkenyl group, or an alkoxy group, R3 represents hydrogen atom, a halogen atom, hydroxyl group, or an alkoxy group, R4 represents hydrogen atom, or an alkyl group, Z1 and Z2 represent hydrogen atom, a halogen atom, hydroxyl group and the like, Z3 represents cyano group, an alkyl group, an alkenyl group and the like, Z4 represents an alkyl group, an alkenyl group, an alkynyl group and the like, and ---- represents a single bond or a double bond], which shows high antitumor effect against cancer cells including drug resistant cells.

  一个由通式（1）表示的化合物，其中[X1和X2代表氢原子，卤素原子，羟基等，R1代表苯基，R2代表烷基，烯基或烷氧基，R3代表氢原子，卤素原子，羟基或烷氧基，R4代表氢原子或烷基，Z1和Z2代表氢原子，卤素原子，羟基等，Z3代表氰基，烷基，烯基等，Z4代表烷基，烯基，炔基等，----代表单键或双键]，对包括药物耐药细胞在内的癌细胞表现出高抗肿瘤效果。
• Method for producing pentacyclic taxans
  申请人：Imura Akihiro

  公开号：US20070167630A1

  公开（公告）日：2007-07-19

  Taxan derivatives are produced efficiently and inexpensively, which are useful as oral-administrable antitumor compounds. A compound of formula (1) (wherein R 1 is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group; R 2 is a hydroxyl group optionally having a protective group) is processed with an alkali metal permanganate to produce a compound of formula (2), which may be a starting material for oral-administrable antitumor compounds.

  Taxan衍生物的生产是高效和廉价的，这些衍生物可作为口服抗肿瘤化合物。将式（1）的化合物（其中R1是烷基，烯基，炔基，环烷基，芳基或杂环基；R2是一个羟基，可选地具有保护基）与碱金属高锰酸盐处理，可产生式（2）的化合物，该化合物可作为口服抗肿瘤化合物的起始物质。
• METHOD FOR PRODUCING PENTACYCLIC TAXANS
  申请人：IMURA Akihiro

  公开号：US20090030209A1

  公开（公告）日：2009-01-29

  Taxan derivatives are produced efficiently and inexpensively, which are useful as oral-administrable antitumor compounds. A compound of formula (1) (wherein R 1 is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group; R 2 is a hydroxyl group optionally having a protective group) is processed with an alkali metal permanganate to produce a compound of formula (2), which may be a starting material for oral-administrable antitumor compounds.

  Taxan衍生物可以高效且低成本地生产，这些衍生物可作为口服抗肿瘤化合物。公式（1）中的化合物（其中R1是烷基，烯基，炔基，环烷基，芳基或杂环基；R2是氢氧基，可选有保护基）与碱金属高锰酸盐反应，可产生公式（2）中的化合物，该化合物可作为口服抗肿瘤化合物的起始物质。
• Taxane Compound Having Azetidine Ring Structure
  申请人：Uoto Kouichi

  公开号：US20090186868A1

  公开（公告）日：2009-07-23

  A compound represented by the general formula (1) [X 1 and X 2 represent hydrogen atom, a halogen atom, hydroxyl group and the like, R 1 represents a phenyl group, R 2 represents an alkyl group, an alkenyl group, or an alkoxy group, R 3 represents hydrogen atom, a halogen atom, hydroxyl group, or an alkoxy group, R 4 represents hydrogen atom, or an alkyl group, Z 1 and Z 2 represent hydrogen atom, a halogen atom, hydroxyl group and the like, Z 3 represents cyano group, an alkyl group, an alkenyl group and the like, Z 4 represents an alkyl group, an alkenyl group, an alkynyl group and the like, and represents a single bond or a double bond], which shows high antitumor effect against cancer cells including drug resistant cells.

  一种化合物由通式（1）表示 [其中X1和X2代表氢原子、卤素原子、羟基等，R1代表苯基，R2代表烷基、烯基或烷氧基，R3代表氢原子、卤素原子、羟基或烷氧基，R4代表氢原子或烷基，Z1和Z2代表氢原子、卤素原子、羟基等，Z3代表氰基、烷基、烯基等，Z4代表烷基、烯基、炔基等，且表示单键或双键]，对包括耐药细胞在内的癌细胞具有高抗肿瘤效果。
• New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 5
  作者：Yasuyuki Takeda、Kouichi Uoto、Michio Iwahana、Takeshi Jimbo、Motoko Nagata、Ryo Atsumi、Chiho Ono、Noriko Tanaka、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.1016/j.bmcl.2004.03.109

  日期：2004.6

  To improve the metabolic stability of 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, we designed and synthesized new taxane analogues. Most of the synthetic compounds maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. And some compounds exhibited potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration similarly to 3. (C) 2004 Elsevier Ltd. All rights reserved.