4-(2-chloroacetyl)piperidine-1-carboxylic acid benzyl ester | 85475-10-1

• 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: 4-(2-chloroacetyl)piperidine-1-carboxylic acid benzyl ester
• 英文别名: benzyl 4-(2-chloroacetyl)piperidine-1-carboxylate；4-(2-chloroacetyl)-N-carbobenzoxypiperidine
• CAS: 85475-10-1
• 化学式: C₁₅H₁₈ClNO₃
• 分子量: 295.766
• InChiKey: BTFDQROQQVEQQD-UHFFFAOYSA-N

物化性质

• 沸点：
  430.7±45.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  4-(2-chloroacetyl)piperidine-1-carboxylic acid benzyl ester 在 ammonium acetate 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 2.58h， 生成 benzyl 4-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-pyrrol-2-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Chemical probes of a trisubstituted pyrrole to identify its protein target(s) in Plasmodium sporozoites

  摘要：

  Malaria is a disease that has a major impact in many developing nations, especially on the African continent. There is a need to develop new therapeutics and prophylactic treatments against it. A trisubstituted pyrrole was recently found to inhibit infection of mammalian hepatocytes by Plasmodium sporozoites, but the target of this agent is not known. In this study trisubstituted pyrrole derivatives with different substituents on a piperidinyl nitrogen were prepared. We determined if modifications of the piperidinyl nitrogen would accommodate a drug-biotin linking strategy for affinity purification of the trisubstituted pyrrole's target protein(s). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.010
• 作为产物：
  描述：

  Benzyl 4-[2-[dimethyl(oxo)-lambda6-sulfanylidene]acetyl]piperidine-1-carboxylate 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 6.0h， 生成 4-(2-chloroacetyl)piperidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  [EN] STEREOSELECTIVE HYDROGENATION OF A KETONE
  [FR] HYDROGÉNATION STÉRÉOSÉLECTIVE D'UNE CÉTONE

  摘要：

  本发明涉及一种方法，包括使用手性选择性加氢剂还原式(I)的酮，形成基本对映纯的式(II)的醇，其中R-R4和m如本文所定义。本发明的方法适用于制备CCR2调节剂以及CCR2调节剂的前体。

  公开号：

  WO2010099098A1

文献信息

• Compounds having cytokine inhibitory activity
  申请人：Merck & Co., Inc.

  公开号：US06350744B1

  公开（公告）日：2002-02-26

  There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which exhibit utility for the treatment of cytokine mediated diseases such as arthritis.

  公开了化合物的结构式（I）及其药学上可接受的盐，其对治疗细胞因子介导的疾病如关节炎具有实用性。
• [EN] SUBSTITUTED PYRIDYL PYRROLES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE<br/>[FR] PYRROLES DE PYRIDYLE SUBSTITUES, COMPOSITIONS CONTENANT DE TELS COMPOSES ET MODE D'UTILISATION
  申请人：MERCK & CO., INC.

  公开号：WO1997016442A1

  公开（公告）日：1997-05-09

  (EN) The present invention addresses substituted pyridyl pyrroles, as well as compositions containing such compounds and methods of treatment. The compounds in the present invention are glucagon antagonists and inhibitors of the biosynthesis and action of TNF-$g(a) and IL1. The compounds block the action of glucagon at its receptors and thereby decrease the levels of plasma glucose. The instant pyrroles are also inhibitors of TNF-$g(a) and IL1 and may be used as antidiabetic agents as well as other cytokine mediated diseases. Cytokine mediated diseases refer to diseases or conditions in which excessive or unregulated production of one or more cytokines occurs. Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) are cytokines produced by a variety of cells, which are involved in immunoregulation and other physiological conditions, such as inflammation.(FR) La présente invention concerne des pyrroles de pyridyle substitués, des compositions contenant de tels composés et leur utilisation thérapeutique. Les composés de la présente invention sont des antagoniste du glucagon et des inhibiteurs de la biosynthèse et de l'action du facteur TNF-$g(a) et de l'IL1. Ces composés bloquent l'action du glucagon au niveau de ses récepteurs, ce qui diminue les niveaux de glucose du plasma. Les pyrroles de l'invention, qui sont également des inhibiteurs du facteur TNF-$g(a) et de l'IL1, peuvent servir d'antidiabétiques et contre d'autres affections à médiation des cytokines. L'interleukine-1 (IL-1) et le facteur de nécrose tumorale (TNF) sont des cytokines produites par diverses cellules qui interviennent au niveau de la régulation immunitaire et au niveau d'autres états physiologiques tels que les états inflammatoires.

  该发明涉及取代的吡啶基吡咯烷，以及包含这些化合物的组合物和治疗方法。本发明中的化合物是胰高血糖素拮抗剂和TNF-$g(a)和IL1的生物合成和作用的抑制剂。这些化合物阻止胰高血糖素在其受体上的作用，从而降低血浆葡萄糖水平。这些吡咯烷也是TNF-$g(a)和IL1的抑制剂，可以用作抗糖尿病剂以及其他细胞因子介导的疾病。细胞因子介导的疾病是指一种或多种细胞因子的过度或失控产生导致的疾病或病症。白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）是由多种细胞产生的细胞因子，参与免疫调节和其他生理条件，如炎症。
• Discovery of 1,3-disubstituted-1H-pyrrole derivatives as potent Melanin-Concentrating Hormone Receptor 1 (MCH-R1) antagonists
  作者：Susanne Berglund、Bryan J. Egner、Henrik Gradén、Joakim Gradén、David G.A. Morgan、Tord Inghardt、Fabrizio Giordanetto

  DOI：10.1016/j.bmcl.2008.07.079

  日期：2008.9

  A series of 1,3-disubstituted-1H-pyrrole-based antagonists of the human Melanin-Concentrating Hormone Receptor 1 (h-MCH-R1) are reported. High-throughput screening of the AstraZeneca compound collection yielded 1, a hit with moderate affinity towards MCH-R1. Subsequent structural manipulations and SAR analysis served to rationalize potency requirements, and 12 was identified as a novel, functional MCH-R1 antagonist with favorable pharmacokinetic properties. (C) 2008 Elsevier Ltd. All rights reserved.
• Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase
  作者：Nuria Tamayo、Lillian Liao、Martin Goldberg、David Powers、Yan-Yan Tudor、Violeta Yu、Lu Min Wong、Bradley Henkle、Scot Middleton、Rashid Syed、Timothy Harvey、Graham Jang、Randall Hungate、Celia Dominguez

  DOI：10.1016/j.bmcl.2005.02.010

  日期：2005.5

  Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.
• Pyridazine based inhibitors of p38 MAPK
  作者：Charles J McIntyre、Gerald S Ponticello、Nigel J Liverton、Stephen J O’Keefe、Edward A O’Neill、Margaret Pang、Cheryl D Schwartz、David A Claremon

  DOI：10.1016/s0960-894x(01)00834-4

  日期：2002.2

  Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38 MAPK. The most active isomers were those possessing an aryl group alpha and a heteroaryl group beta relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC50 1-20 nM) in vitro activity. (C) 2002 Elsevier Science Ltd. All rights reserved.