2-(3-氯丙基)-乙酰乙酸乙酯 | 99054-01-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 2-(3-氯丙基)-乙酰乙酸乙酯
• 英文名称: ethyl 7-chloro-3-oxoheptanoate
• 英文别名: 2-(3-chloropropyl)-acetoacetic acid ethyl ester
• CAS: 99054-01-0
• 化学式: C₉H₁₅ClO₃
• 分子量: 206.669
• InChiKey: OXPOIABOXLXYKI-UHFFFAOYSA-N

物化性质

• 沸点：
  89-90 °C(Press: 0.05 Torr)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-氯丙基)-乙酰乙酸乙酯 在 sodium azide 、 potassium carbonate 、 三苯基膦 、 sodium iodide 作用下， 以 乙醚 、 二甲基亚砜 、 丙酮 为溶剂， 反应 62.0h， 生成 ethyl 2-(piperidin-2-ylidene)propanoate
  参考文献：
  名称：

  Application of the intramolecular aza-Wittig reaction to the synthesis of vinylogous urethanes and amides

  摘要：

  DOI：

  10.1021/jo00225a066
• 作为产物：
  描述：

  1-氯-3-碘丙烷 、 乙酰乙酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以55%的产率得到2-(3-氯丙基)-乙酰乙酸乙酯
  参考文献：
  名称：

  基于 4-烷基-和 4-氯烷基-1,3-双(三甲基甲硅烷氧基)丁-1,3-二烯的 [3+3] 环化合成 3-烷基-和 3-氯烷基-2-羟基苯甲酸酯

  摘要：

  TiCl 4 介导的 [3+3] 环化 4-烷基-和 4-氯烷基-1,3-双(三甲基甲硅烷氧基)丁-1,3-二烯与 3-甲硅烷基-烷-2-烯-1-酮分别得到3-烷基-和3-氯烷基-2-羟基苯甲酸酯；后者包含远程氯化物功能。TiCl 4 - 和TiBr 4 介导的1,3-双(三甲基甲硅烷氧基)-4-氯烷基丁-1,3-二烯与1,1-二乙酰环丙烷的[3+3] 环化反应得到含有两个远程卤化物官能团的水杨酸盐。

  DOI：

  10.1055/s-2006-926381

文献信息

• [EN] 2-ACYLAMIDOMETHYL AND SULFONYLAMIDOMETHYL BENZOXAZINE CARBAMATES FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE<br/>[FR] BENZOXAZINE CARBAMATES DE 2-ACYLAMIDOMÉTHYLE ET DE SULFONYLAMIDOMÉTHYLE POUR L'INHIBITION DE L'ACTIVITÉ DU RORGAMMA ET LE TRAITEMENT D'UNE MALADIE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015095788A1

  公开（公告）日：2015-06-25

  The invention provides certain benzoxazine compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, Ra, Rb, Rc, Rd, Rg, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.

  该发明提供了Formula (I)的某些苯并噁嗪化合物或其药用盐，其中R1、R2、Ra、Rb、Rc、Rd、Rg和Cy如本文所定义。该发明还提供了包括Formula (I)的这些化合物或其药用盐的药物组合物，以及使用Formula (I)的这些化合物或其药用盐或包含相同的药物组合物治疗由RORgammaT介导的疾病或症状的方法。
• N-heterocyclic derivatives as NOS inhibitors
  申请人：Berlex Laboratories, Inc.

  公开号：US06432947B1

  公开（公告）日：2002-08-13

  N-Heterocyclic derivatives of the formula (I): are described herein, as well as other N-heterocycles, as inhibitors of nitric oxide synthase. Pharmaceutical compositions containing these compounds, methods of using these compounds as inhibitors of nitric oxide synthase and processes for synthesizing these compounds are also described herein.

  本文描述了公式（I）的N-杂环衍生物，以及其他N-杂环化合物，作为一氧化氮合酶的抑制剂。本文还描述了含有这些化合物的药物组合物，使用这些化合物作为一氧化氮合酶抑制剂的方法，以及合成这些化合物的过程。
• The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A
  作者：Egils Bisenieks、Brigita Vigante、Ramona Petrovska、Baiba Turovska、Ruslan Muhamadejev、Vitalijs Soloduns、Astrida Velena、Karlis Pajuste、Luciano Saso、Janis Klovins、Gunars Duburs、Ilona Mandrika

  DOI：10.3390/ph14100987

  日期：——

  The paradigm of ligand-receptor interactions postulated as “one compound—one target” has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.

  配体-受体相互作用范式被提出为“一个化合物-一个靶标”，正在演变；多靶点、多效应途径现在被认为是现实的。为了表征它们在FFA3/GPR41、FFA2/GPR43和HCA2/GPR109A受体上的多效应、多靶点活性，已经合成了新的1,4,5,6,7,8-六氢-5-氧喹啉、吡喃吡嘧啶和吡喃吡嘧啶的S-烷基衍生物系列。已知六氢喹啉衍生物表现出作为FFA3/GPR41配体的特征活性，但在这项研究中，我们观察到它们对FFA2/GPR43和HCA2/GPR109A受体的影响，以及它们的电子给体活性。氧代吡喃吡嘧啶和硫代吡喃吡嘧啶类化合物已被研究为HCA2/GPR109A受体的配体；然而，它们表现出对FFA3/GPR41和FFA2/GPR43受体相同或更高的活性。尚未作为GPCR配体研究的吡喃吡嘧啶的S-烷基衍生物对HCA2/GPR109A和FFA3/GPR41受体的活性比对FFA2/GPR43更高。每个合成系列的代表性化合物能够降低THP-1巨噬细胞中脂多糖诱导的炎症细胞因子（IL-6、TNF-α）和趋化因子（MCP-1）的基因表达和分泌，类似于HCA2/GPR109A配体烟酸和内源性配体丙酸的作用。这项研究揭示了一些具有多靶点活性的化合物群。获得的数据对于进一步开发多靶点配体可能是有用的。
• Synthesis of 3-Acylpyrroles, 3-(Alkoxycarbonyl)pyrroles, 1,5,6,7-Tetrahydro-4H-indol-4-ones and 3-Benzoylpyridines Based on Staudinger-Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds with 2- and 3-Azido-1,1-dialkoxy­alkanes
  作者：Peter Langer、Esen Bellur、Mirza Yawer、Ibrar Hussain、Abdolmajid Riahi、Olumide Fatunsin、Christine Fischer

  DOI：10.1055/s-0028-1083285

  日期：2009.1

  The Staudinger-aza-Wittig reaction of 1,3-dicarbonyl compounds with 2-azido-1,1-diethoxyethane and subsequent cyclization allowed an efficient synthesis of a variety of pyrroles, 1,5,6,7-tetrahydro-4H-indol-4-ones, and of a pyridine. cyclization - N-heterocycles - pyrroles - azides

  的1,3-二羰基化合物与2-叠氮基-1,1-二乙氧基乙烷和随后的环化的施陶丁格氮杂- Wittig反应允许的各种吡咯，1,5,6,7-四氢-4-一种高效合成ħ -吲哚-4-酮和吡啶。 环化-N-杂环-吡咯-叠氮化物
• [EN] CARBAMATE BENZOXAXINE PROPIONIC ACIDS AND ACID DERIVATIVES FOR MODULATION OF RORGAMMA ACTIVITY AND THE TREATMENT OF DISEASE<br/>[FR] ACIDES PROPIONIQUES DE CARBAMATE BENZOXAZINE ET DÉRIVÉS ACIDES POUR LA MODULATION DE L'ACTIVITÉ DE RORGAMMA ET LE TRAITEMENT DE MALADIE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015095792A1

  公开（公告）日：2015-06-25

  The invention provides certain benzoxazine compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, Ra1, Ra2, Rb1, Rb2, Rc, Rd, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.

  该发明提供了一些苯并噁嗪化合物的结构式（I）或其药学上可接受的盐，其中R1、R2、Ra1、Ra2、Rb1、Rb2、Rc、Rd和Cy如本文所定义。该发明还提供了包括该结构式（I）化合物或其药学上可接受的盐的药物组合物，以及使用该结构式（I）化合物或其药学上可接受的盐或包含相同的药物组合物治疗由RORgammaT介导的疾病或症状的方法。