methyl 9-bromo-8-oxononanoate | 124475-55-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 9-bromo-8-oxononanoate
• CAS: 124475-55-4
• 化学式: C₁₀H₁₇BrO₃
• 分子量: 265.147
• InChiKey: PKDSDYROVMAKDK-UHFFFAOYSA-N

物化性质

• 沸点：
  324.2±22.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  methyl 9-bromo-8-oxononanoate 在 三甲基氯硅烷 、 sodium acetate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 148.5h， 生成 4-Oxoundecandioic Acid Dimethyl Ester
  参考文献：
  名称：

  Synthesis of 5-alkylidene-2-pyrrolidinones

  摘要：

  DOI：

  10.1007/bf00955460
• 作为产物：
  描述：

  辛二酸单甲酯 在 草酰氯 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.67h， 生成 methyl 9-bromo-8-oxononanoate
  参考文献：
  名称：

  Tumor-Targeting with Novel Non-Benzoyl 6-Substituted Straight Chain Pyrrolo[2,3-d]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and Inhibition of de Novo Purine Nucleotide Biosynthesis

  摘要：

  A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the alpha-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl L-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FR alpha and -beta, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FR alpha.

  DOI：

  10.1021/jm401139z

文献信息

• A novel series of histone deacetylase inhibitors incorporating hetero aromatic ring systems as connection units
  作者：Yujia Dai、Yan Guo、Michael L. Curtin、Junling Li、Lori J. Pease、Jun Guo、Patrick A. Marcotte、Keith B. Glaser、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1016/j.bmcl.2003.07.012

  日期：2003.11

  A series of structurally novel HDAC inhibitors, in which a hetero aromatic ring connects the spacer with the hydrophobic group, has been designed and synthesized. These new inhibitors are very potent in in vitro enzymatic assays and display antiproliferation activity against two human cancer cell lines. (C) 2003 Elsevier Ltd. All rights reserved.
• ZAVYALOV, S. I.;KRAVCHENKO, N. E., IZV. AN CCCP. CEP. XIM.,(1989) N, S. 1195-1198
  作者：ZAVYALOV, S. I.、KRAVCHENKO, N. E.

  DOI：——

  日期：——
• DERIVATIVES OF MONIC ACIDS A AND C HAVING ANTIBACTERIAL, ANTIMYCOPLASMATICAL, ANTIFUNGAL AND HERBICIDAL ACTIVITY
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0712405A1

  公开（公告）日：1996-05-22
• [EN] DERIVATIVES OF MONIC ACIDS A AND C HAVING ANTIBACTERIAL, ANTIMYCOPLASMATICAL, ANTIFUNGAL AND HERBICIDAL ACTIVITY<br/>[FR] DERIVES D'ACIDES MONIQUES A ET C A ACTIVITE ANTIBACTERIENNE, ANTIMYCOPLASMIQUE, ANTIFONGIQUE ET HERBICIDE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1995005384A1

  公开（公告）日：1995-02-23

  (EN) Derivatives of monic acids A and C of formula (I) in which: A is an epoxy moiety or an E-double bond moiety: (i) or (ii); B is selected from (a), (b), (c) (which corresponds to C(OH)=CHCO-B3), (d) in which Q denotes the residue of an optionally substituted aryl or heteroaryl ring; D is a group of atoms for linking B with -CONR1; or B-D represents (E)-C(CH3)=CH; and R1 and R2, which may be the same or different, is each selected from hydrogen or (C1-6)alkyl, (C3-7)cycloalkyl, (C2-6)alkenyl, aryl, aryl(C1-4)alkyl, heterocyclyl, (C1-6)alkylcarbonyl, (C3-7)cycloalkylcarbonyl, (C2-6)alkenylcarbonyl, arylcarbonyl, aryl(C1-4)alkylcarbonyl or heterocyclylcarbonyl, each of which may be optionally substituted, have useful antibacterial, antimycoplasmal, antifungal and herbicidal activity.(FR) Dérivés d'acides moniques A et C de la formule (I), dans laquelle A représente une fraction époxy ou une fraction à liaison double-E (i) ou (ii); B est choisi entre (a), (b), (c) et (d) (qui correspond à C(OH)=CHCO-B3), Q représentant le reste d'un noyau aryle ou hétéroaryle éventuellement substitué; D représente un groupe d'atomes liant B à -CONR1; ou B-D représentent (E)-C(CH3)=CH; et R1 et R2, qui peuvent être identiques ou différents, sont chacun choisis entre hydrogène ou (C1-6)alkyle, (C3-7)cycloalkyle, (C2-6)alcényle, aryle, aryl(C1-4)alkyle, hétérocyclyle, (C1-6)alkylcarbonyle, (C3-7)cycloalkylcarbonyle, (C2-6)alcénylcarbonyle, arylcarbonyle, aryl(C1-4)alkylcarbonyle ou hétérocyclylcarbonyle, dont chacun peut éventuellement être substitué. Ces dérivés présentent une activité antibactérienne, antimycoplasmique, antifongique et herbicide.
• Tumor-Targeting with Novel Non-Benzoyl 6-Substituted Straight Chain Pyrrolo[2,3-<i>d</i>]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and Inhibition of de Novo Purine Nucleotide Biosynthesis
  作者：Yiqiang Wang、Christina Cherian、Steven Orr、Shermaine Mitchell-Ryan、Zhanjun Hou、Sudhir Raghavan、Larry H. Matherly、Aleem Gangjee

  DOI：10.1021/jm401139z

  日期：2013.11.14

  A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the alpha-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl L-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FR alpha and -beta, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FR alpha.