n-propyl 4-oxopiperidine-1-carboxylate | 1078692-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: n-propyl 4-oxopiperidine-1-carboxylate
• 英文别名: Propyl 4-oxopiperidine-1-carboxylate
• CAS: 1078692-25-7
• 化学式: C₉H₁₅NO₃
• 分子量: 185.223
• InChiKey: WMRJPTHLEMTNCL-UHFFFAOYSA-N

物化性质

• 沸点：
  289.0±33.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  n-propyl 4-oxopiperidine-1-carboxylate 在 四氢吡咯 、 titanium(IV) tetraethanolate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 28.0h， 生成 C₂₁H₂₉BrN₂O₄S
  参考文献：
  名称：

  DNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors

  摘要：

  We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane 1, had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead 11. Although amorphous 11 was highly bio-available, crystalline 11 was poorly soluble and suffered disappointingly low bio-availability because of solubility-limited absorption. A prodrug approach was deployed and proved effective in discovering the highly bio-available phosphonooxymethyl 31, which rapidly converted to 11 in vivo. Obtaining crystalline 31 proved problematic, however; thus salt screening was performed in an attempt to circumvent this obstacle and successfully delivered greatly soluble and bio-available crystalline tris-salt 32. IDO1 inhibitor 32 is characterized by a low calculated human dose, best-in-class potential, and an unusual inhibition mode by binding the IDO1 heme-free (apo) form.

  DOI：

  10.1021/acs.jmedchem.9b01799
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 氯甲酸丙酯 在 potassium carbonate 作用下， 以 水 为溶剂， 反应 2.0h， 以78%的产率得到n-propyl 4-oxopiperidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-6-substituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives as antimitotic agents and inhibitors of tubulin polymerization

  摘要：

  Microtubules are among the most successful targets of compounds potentially useful for cancer therapy. A new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine, which inhibits cancer cell growth with IC50-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N-6-carbamate derivatives, any further increase in the length and in the size of the alkyl chain resulted in reduced activity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.006