2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride

• 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: 2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride
• 英文别名: 1-(4-Aminopiperidin-1-yl)-2-hydroxyethanone hydrochloride；1-(4-aminopiperidin-1-yl)-2-hydroxyethanone;hydrochloride
• 化学式: C₇H₁₄N₂O₂*ClH
• 分子量: 194.661
• InChiKey: XIUCLELTNHRQDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.65
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  66.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 2-ethyl-3-[2-(4-fluorophenyl)-2-oxoethyl]-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF

  摘要：

  公开号：

  EP2471793B1
• 作为产物：
  描述：

  [2-(4-aminopiperidin-1-yl)-2-oxoethyl] acetate 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以3.73 g的产率得到2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride
  参考文献：
  名称：

  Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: Modification of the core skeleton for improved solubility

  摘要：

  We recently reported the discovery of the novel pyrrolo[3,2-c] quinoline-4-one derivative 1 as a potent inhibitor of Hedgehog (Hh) pathway signaling. However, the PK evaluation of 1 at high dosage (100 mg/kg) revealed the C-max value 3.63 mu g/mL, likely due to poor solubility of this compound. Efforts to improve solubility by reducing the aromatic ring count of the core system led to N-methylpyrrolo[3,2-c]pyridine derivative 11. Further optimization of the 3-alkoxy group led to compound 11d with acceptable solubility and potent Hh inhibitory activity. Compound 11d suppressed transcription factor Gli1 mRNA expression in tumor-associated stromal tissue and inhibited tumor growth (treatment/control ratio, 3%) in a mouse medulloblastoma allograft model owing to the improved PK profile based on increased solubility. Compound 11d (TAK-441) is currently in clinical trials for the treatment of advanced solid tumors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.034

文献信息

• FUSED HETEROCYCLIC DERIVATIVE AND USE THEREOF
  申请人：FUJII Nobuhiro

  公开号：US20090227561A1

  公开（公告）日：2009-09-10

  The present invention provides a compound having a superior Smo inhibitory activity and lower toxicity, which is sufficiently satisfactory as a pharmaceutical product. The present invention provides a compound represented by the formula wherein ring A is 5- to 7-membered ring optionally having substituent(s), where substituents are optionally bonded to each other to form a ring; X is O, S or NR 1 (R 1 is a hydrogen atom or a hydrocarbon group optionally having substituent(s)); R 2 is carbamoyl optionally having substituent(s); and R 3 is hydroxy optionally having substituent(s), or a salt thereof.

  本发明提供了一种具有优异的Smo抑制活性和较低毒性的化合物，该化合物作为药物产品是完全令人满意的。本发明提供了一种由下式表示的化合物： 其中，环A是5-至7-成员环，可选择地具有取代基，其中取代基可选择地与彼此结合形成环；X是O、S或NR1（R1是氢原子或具有取代基的碳氢基团）；R2是氨基甲酰，可选择地具有取代基；R3是羟基，可选择地具有取代基，或其盐。
• Fused heterocyclic ring derivative and use thereof
  申请人：Banno Hiroshi

  公开号：US08614208B2

  公开（公告）日：2013-12-24

  The present invention provides a fused heterocycle derivative having a strong Smo inhibitory activity, and use thereof. Specially, the present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or salt thereof, and a medicament containing the compound or a prodrug thereof, which is an Smo inhibitor or an agent for the prophylaxis or treatment of cancer.

  本发明提供了一种具有强烈Smo抑制活性的融合杂环衍生物及其使用。特别是，本发明涉及一种由式子表示的化合物，其中每个符号如规范中定义的，或其盐，以及含有该化合物或其前药的药物，其为Smo抑制剂或预防或治疗癌症的药剂。
• Synthesis and evaluation of hedgehog signaling inhibitor with novel core system
  作者：Tomohiro Ohashi、Yuta Tanaka、Zenyu Shiokawa、Hiroshi Banno、Toshio Tanaka、Sachio Shibata、Yoshihiko Satoh、Hiroko Yamakawa、Yukiko Yamamoto、Harumi Hattori、Shigeru Kondo、Maki Miyamoto、Hideaki Tojo、Atsuo Baba、Satoshi Sasaki

  DOI：10.1016/j.bmc.2015.05.036

  日期：2015.8

  As we previously reported, N-methylpyrrolo[3,2-c] pyridine derivatives 1 (TAK-441) was discovered as a clinical candidate of hedgehog (Hh) signaling inhibitor by modification of the upper part. We next focused on modification of the lower part including core skeletons to discover new Hh signaling inhibitors with novel core rings. Efforts to find novel chemotypes by using X-ray single crystal structure analysis led to some potent Hh signaling inhibitors (2c, 2d, 2e, 2f) with novel core ring systems, which had benzamide moiety at the 5-position as a key component for potent activity. The suppression of Gli1 expression with these new Hh signaling inhibitors were weaker than that of compound 1 (TAK-441) because of low pharmacokinetic property. We recognized again TAK-441 is a good compound as clinical candidate with good structural and pharmacokinetic advantages. (C) 2015 Elsevier Ltd. All rights reserved.
• US8217176B2
  申请人：——

  公开号：US8217176B2

  公开（公告）日：2012-07-10
• US8399449B2
  申请人：——

  公开号：US8399449B2

  公开（公告）日：2013-03-19