dimethyl 2-(6-chloronicotinoyl)malonate | 923034-23-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: dimethyl 2-(6-chloronicotinoyl)malonate
• 英文别名: Dimethyl 2-(6-chloronicotinoyl)malonate；dimethyl 2-(6-chloropyridine-3-carbonyl)propanedioate
• CAS: 923034-23-5
• 化学式: C₁₁H₁₀ClNO₅
• 分子量: 271.657
• InChiKey: QYOPTGFIERTTST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 2-(6-chloronicotinoyl)malonate 以 水 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 1-(6-methylaminopyridin-3-yl)ethanone
  参考文献：
  名称：

  5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure–activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors

  摘要：

  4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.023
• 作为产物：
  描述：

  6-氯吡啶-3-羰酰氯 、 丙二酸二甲酯 以 甲苯 为溶剂， 生成 dimethyl 2-(6-chloronicotinoyl)malonate
  参考文献：
  名称：

  氯化镁催化的酰化反应

  摘要：

  描述了一种在叔碱存在下，通过氯化镁催化的丙二酸二甲酯与酰氯的酰化反应，然后脱碳甲氧基化反应的一种有效而实用的制备甲基酮的方法。

  DOI：

  10.1016/s0040-4020(01)85613-1

文献信息

• Multicyclic sulfonamide compounds as inhibitors of histone deacetylase for the treatment of disease
  申请人：Malecha W. James

  公开号：US20070027184A1

  公开（公告）日：2007-02-01

  Disclosed herein are sulfonamide compounds of Formula VII as described herein. Methods and compositions are disclosed for treating disease states including, but not limited to cancers, autoimmune diseases, tissue damage, central nervous system disorders, neurodegenerative disorders, fibrosis, bone disorders, polyglutamine-repeat disorders, anemias, thalassemias, inflammatory conditions, cardiovascular conditions, and disorders in which angiogenesis play a role in pathogenesis, using the compounds of the invention. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.

  本文披露了如下所述的Formula VII的磺胺类化合物。本文还披露了用于治疗疾病状态的方法和组合物，包括但不限于癌症、自身免疫疾病、组织损伤、中枢神经系统疾病、神经退行性疾病、纤维化、骨疾病、多聚谷氨酰胺重复疾病、贫血、地中海贫血、炎症症状、心血管疾病以及血管生成在发病机制中起作用的疾病，使用本发明的化合物。此外，还披露了调节组蛋白去乙酰化酶（HDAC）活性的方法。
• Magnesium chloride catalysed acylation reaction
  作者：David L. Kuo

  DOI：10.1016/s0040-4020(01)85613-1

  日期：1992.1

  An efficient and practical preparation of methyl ketones, via a magnesium chloride catalysed acylation reaction of dimethyl malonate with acid chlorides in the presence of tertiary base and followed by a decarbmethoxylation reaction, is described.

  描述了一种在叔碱存在下，通过氯化镁催化的丙二酸二甲酯与酰氯的酰化反应，然后脱碳甲氧基化反应的一种有效而实用的制备甲基酮的方法。
• Adenosine kinase inhibitors: polar 7-Substitutent of pyridopyrimidine derivatives improving their locomotor selectivity
  作者：Guo Zhu Zheng、Yue Mao、Chih-Hung Lee、John K. Pratt、John R. Koenig、Richard J. Perner、Marlon D. Cowart、Gregory A. Gfesser、Steve McGaraughty、Katharine L. Chu、Chang Zhu、Haixia Yu、Kathy Kohlhaas、Karen M. Alexander、Carol T. Wismer、Joseph Mikusa、Michael F. Jarvis、Elizabeth A. Kowaluk、Andrew O. Stewart

  DOI：10.1016/s0960-894x(03)00642-5

  日期：2003.9

  We have discovered that polar 7-substituents of pyridopyrimidine derivatives affect not only whole cell AK inhibitory potency. but also selectivity in causing locomotor side effects in vivo animal models. We have identified compound, 1o, which has potent whole cell AK inhibitory potency, analgesic activity and minimal reduction of locomotor activity. (C) 2003 Elsevier Ltd. All rights reserved.
• α-Mercaptoketone based histone deacetylase inhibitors
  作者：Paul L. Wash、Timothy Z. Hoffman、Brandon M. Wiley、Céline Bonnefous、Nicholas D. Smith、Michael S. Sertic、Charles M. Lawrence、Kent T. Symons、Phan-Manh Nguyen、Kevin D. Lustig、Xin Guo、Tami Annable、Stewart A. Noble、Jeffrey H. Hager、Christian A. Hassig、James W. Malecha

  DOI：10.1016/j.bmcl.2008.10.058

  日期：2008.12

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.
• MULTICYCLIC SULFONAMIDE COMPOUNDS AS INHIBITORS OF HISTONE DEACETYLASE FOR THE TREATMENT OF DISEASE
  申请人：Kalypsys, Inc.

  公开号：EP1910342A1

  公开（公告）日：2008-04-16