3-iodomethyl-cyclopentanone | 71987-94-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-iodomethyl-cyclopentanone
• 英文别名: 3-(Iodomethyl)cyclopentan-1-one；3-(iodomethyl)cyclopentanone；3-iodomethylcyclopentanone
• CAS: 71987-94-5
• 化学式: C₆H₉IO
• 分子量: 224.041
• InChiKey: FVUGNUPDVVXVPU-UHFFFAOYSA-N

物化性质

• 沸点：
  252.6±13.0 °C(Predicted)
• 密度：
  1.790±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-iodomethyl-cyclopentanone 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以59%的产率得到3-iodomethyl-cyclopentanol
  参考文献：
  名称：

  Substituted-cycloalkyl and oxygenated-cycloalkyl glucokinase activators

  摘要：

  2,3-二取代N-杂环丙酰胺，其中2-位置的取代物是取代苯基，3-位置的取代物是极性环，这些丙酰胺是葡萄糖激酶激活剂，可增加胰岛素分泌，用于治疗2型糖尿病。

  公开号：

  US20030225283A1
• 作为产物：
  描述：

  2-环戊烯酮 在 三甲基氯硅烷 、 sodium hydride 、 sodium iodide 作用下， 以 二甲基亚砜 、 乙腈 、 mineral oil 为溶剂， 反应 48.0h， 生成 3-iodomethyl-cyclopentanone
  参考文献：
  名称：

  Substituted pyrazolones require N2 hydrogen bond donating ability to protect against cytotoxicity from protein aggregation of mutant superoxide dismutase 1

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease. Although the cause remains unknown, misfolded protein aggregates are seen in neurons of sporadic ALS patients, and familial ALS mutations, including mutations in superoxide dismutase 1 (SOD1), produce proteins with an increased propensity to misfold and aggregate. A structure activity relationship of a lead scaffold exhibiting neuroprotective activity in a G93A-SOD1 mouse model for ALS has been further investigated in a model PC12 cellular assay. Synthesis of biotinylated probes at the N-1 nitrogen of the pyrazolone ring gave compounds (5d-e) that retained activity within 10-fold of the proton-bearing lead compound (5a) and were equipotent with a sterically less cumbersome N-1-methyl substituted analogue (5b). However, when methyl substitution was introduced at N-1 and N-2 of the pyrazolone ring, the compound was inactive (5c). These data led us to investigate further the pharmacophoric nature of the pyrazolone unit. A range of N-1 substitutions were tolerated, leading to the identification of an N-1-benzyl substituted pyrazolone (5m), equipotent with 5a. Substitution at N-2 or excision of N-2, however, removed all activity. Therefore, the hydrogen bond donating ability of the N-2-H of the pyrazolone ring appears to be a critical part of the structure, which will influence further analogue synthesis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.114

文献信息

• [EN] SUBSTITUTED PHENYLACETAMIDES AND THEIR USE AS GLUCOKINASE ACTIVATORS<br/>[FR] ACTIVATEURS DE GLUCOKINASE OXYGENES CYCLOALKYLE OU SUBSTITUES CYCLOALKYLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2003095438A1

  公开（公告）日：2003-11-20

  Compounds of the formula (I); wherein formula (II) represents a substituted group, an oxa-cycloalkyl group or a thia-cycloalkyl group, are glucokinase activators useful in the treatment of type II diabetes.

  式(I)的化合物；其中式(II)代表取代基团，氧杂环烷基团或硫杂环烷基团，是一种在治疗II型糖尿病中有用的葡萄糖激酶激活剂。
• A facile synthesis of bicyclo[m.n.1]alkan-1-ols. Evidence for organosamarium intermediates in the samarium(II) iodide promoted intramolecular Barbier-type reaction
  作者：Gary A. Molander、Jeffrey A. McKie

  DOI：10.1021/jo00013a008

  日期：1991.6

  Samarium(II) iodide (SmI2) has been successfully employed as a reductive coupling agent for the intramolecular Barbier-type synthesis of bicyclo[m.n.1]alkan-1-ols. Thus, a variety of 3-(omega-iodoalkyl)cycloalkanones, upon treatment with SmI2 and a catalytic quantity of iron complex in tetrahydrofuran (THF), provide the title compounds in excellent yields. The reaction is quite general for the construction of diverse bicyclic ring systems, including the highly strained bicyclo[2.1.1]hexan-1-ol. In addition to exploring the synthetic utility of this reaction, studies have been performed which provide insight on the mechanistic details of the SmI2-promoted intramolecular Barbier-type synthesis. Compelling evidence for the intermediacy of organosamarium species has thus been gathered.
• Discovery of Piragliatin—First Glucokinase Activator Studied in Type 2 Diabetic Patients
  作者：Ramakanth Sarabu、Fred T. Bizzarro、Wendy L. Corbett、Mark T. Dvorozniak、Wanping Geng、Joseph F. Grippo、Nancy-Ellen Haynes、Stanley Hutchings、Lisa Garofalo、Kevin R. Guertin、Darryl W. Hilliard、Marek Kabat、Robert F. Kester、Wang Ka、Zhenmin Liang、Paige E. Mahaney、Linda Marcus、Franz M. Matschinsky、David Moore、Jagdish Racha、Roumen Radinov、Yi Ren、Lida Qi、Michael Pignatello、Cheryl L. Spence、Thomas Steele、John Tengi、Joseph Grimsby

  DOI：10.1021/jm3008689

  日期：2012.8.23

  Glucokinase (GK) activation as a potential strategy to treat type 2 diabetes (T2D) is well recognized. Compound 1, a glucokinase activator (GKA) lead that we have previously disclosed, caused reversible hepatic lipidosis in repeat-dose toxicology studies. We hypothesized that the hepatic lipidosis was due to the structure-based toxicity and later established that it was due to the formation of a thiourea metabolite, 2. Subsequent SAR studies of 1 led to the identification of a pyrazine-based lead analogue 3, lacking the thiazole moiety. In vivo metabolite identification studies, followed by the independent synthesis and profiling of the cyclopentyl keto- and hydroxyl- metabolites of 3, led to the selection of piragliatin, 4, as the clinical lead. Piragliatin was found to lower pre- and postprandial glucose levels, improve the insulin secretory profile, increase beta-cell sensitivity to glucose, and decrease hepatic glucose output in patients with T2D.
• Ring opening of cyclopropyl ketones by trimethylsilyl iodide
  作者：Robert D. Miller、Dennis R. McKean

  DOI：10.1021/jo00324a048

  日期：1981.5
• Pyridinium halides as reagents: ring fission modes in .alpha.-cyclopropyl ketones and oximes
  作者：E. Giacomini、M. A. Loreto、L. Pellacani、P. A. Tardella

  DOI：10.1021/jo01291a030

  日期：1980.2