(2S,3S)-3-azido-1,2-O-isopropylidene-1,2,4-butanetriol | 136599-20-7

• 分子结构分类: 有机化合物
• 英文名称: (2S,3S)-3-azido-1,2-O-isopropylidene-1,2,4-butanetriol
• 英文别名: 2-azido-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)ethanol；2-azido-2-(2,2-dimethyl[1,3]dioxolan-4-yl)ethanol；(2S)-2-azido-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanol
• CAS: 136599-20-7
• 化学式: C₇H₁₃N₃O₃
• 分子量: 187.199
• InChiKey: NJBYIXHQMYUHRG-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.81
• 重原子数：
  13.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87.45
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-azido-1,2-O-isopropylidene-1,2,4-butanetriol 在 1,3-丙二硫醇 、 三乙胺 、 silver(l) oxide 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 甲苯 为溶剂， 反应 65.17h， 生成
  参考文献：
  名称：

  Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes

  摘要：

  A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC50 values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.039
• 作为产物：
  描述：

  (2S,3S)-3-azido-1,2,4-butanetriol 、 2,2-二甲氧基丙烷 在 camphorsulfonic acid 作用下， 以 丙酮 为溶剂， 反应 44.0h， 以76%的产率得到(2S,3S)-3-azido-1,2-O-isopropylidene-1,2,4-butanetriol
  参考文献：
  名称：

  [EN] ASPARTYL PROTEASE INHIBITORS
  [FR] INHIBITEURS D'ASPARTYL PROTÉASE

  摘要：

  公式（I）的化合物为：N-氧化物、加合盐、季铵盐金属配合物立体化学异构体及其代谢物，其中A为CR1或N；D为H、C1-C6烷基、C2-C6烯基、C2-C6炔基或Q为C2-C6烯基、C2-C6炔基、芳基或杂环基；W为H、C1-C6烷基、C2-C6烯基、卤代C1-C3烷基、羟基C1-C3烷基、C3-C6环烷基、芳基或杂环基；X'和X"中的一个为H或CH3，另一个为C1-C3烷基、F、OH、NRaRb、CF3或N3；或X'和X"都是F；Y为键、CH2、NRa、O、CH2CH2、CH2NRa、CH2O或S(=O)r；Z为O、S(=O)r或NRa；其他变量如规范中所定义。该发明的化合物是BACE的抑制剂，可用于治疗和/或预防与BACE活性相关的疾病，如阿尔茨海默病。

  公开号：

  WO2010042030A1

文献信息

• Mori, Kenji; Kinsho, Takeshi, Liebigs Annalen der Chemie, 1991, # 12, p. 1309 - 1316
  作者：Mori, Kenji、Kinsho, Takeshi

  DOI：——

  日期：——
• A Novel Pyrazolo[1,5-<i>a</i>]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human Tumor Xenografts Following Oral Administration
  作者：Dean A. Heathcote、Hetal Patel、Sebastian H. B. Kroll、Pascale Hazel、Manikandan Periyasamy、Mary Alikian、Seshu K. Kanneganti、Ashutosh S. Jogalekar、Bodo Scheiper、Marion Barbazanges、Andreas Blum、Jan Brackow、Alekasandra Siwicka、Robert D. M. Pace、Matthew J. Fuchter、James P. Snyder、Dennis C. Liotta、Paul. S. Freemont、Eric O. Aboagye、R. Charles Coombes、Anthony G. M. Barrett、Simak Ali

  DOI：10.1021/jm100732t

  日期：2010.12.23

  Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC50 = 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G(2)/M phases. Consistent with these findings, 4k demonstrated potent antiproliferative activity in 60 cancer cell lines tested (mean GI(50) = 280 nmol/L). Pharmacokinetic studies showed that 4k is orally bioavailable, with an elimination half-life of 178 min following oral dosing in mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human tumor xenografts and suppressed CDK substrate phosphorylation. These findings identify 4k as a novel, potent CDK selective inhibitor with potential for oral delivery in cancer patients.