2-(3-Phenyl-prop-2-ynyloxy)-isoindole-1,3-dione | 188720-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(3-Phenyl-prop-2-ynyloxy)-isoindole-1,3-dione
• 英文别名: 2-(3-Phenylprop-2-ynoxy)isoindole-1,3-dione；2-(3-phenylprop-2-ynoxy)isoindole-1,3-dione
• CAS: 188720-10-7
• 化学式: C₁₇H₁₁NO₃
• 分子量: 277.279
• InChiKey: MXUJSIOHNXXWJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  2-(3-Phenyl-prop-2-ynyloxy)-isoindole-1,3-dione 在 碳酸氢钠 、 一水合肼 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 1.5h， 生成 ethyl N-(3-phenylprop-2-ynoxy)carbamate
  参考文献：
  名称：

  Iodocyclization of Hydroxylamine Derivatives Based on the Control of Oxidative Aromatization Leading to 2,5-Dihydroisoxazoles and Isoxazoles

  摘要：

  An efficient method for the synthesis of 2,5-dihydroisoxazoles and isoxazoles using iodocyclization of N-alkoxycarbonyl O-propargylic hydroxylamines has been developed. 2,5-Dihydro-4-iodoisoxazole underwent the cross-coupling reactions without aromatization to afford polyfunctionalized 2,5-dihydroisoxazoles. This process was applied to the preparation of valdecoxib and its 2,5-dihydro-derivative.

  DOI：

  10.1021/jo200407b
• 作为产物：
  描述：

  3-苯基-2-丙炔-1-醇 在 溴 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(3-Phenyl-prop-2-ynyloxy)-isoindole-1,3-dione
  参考文献：
  名称：

  Iodocyclization of Hydroxylamine Derivatives Based on the Control of Oxidative Aromatization Leading to 2,5-Dihydroisoxazoles and Isoxazoles

  摘要：

  An efficient method for the synthesis of 2,5-dihydroisoxazoles and isoxazoles using iodocyclization of N-alkoxycarbonyl O-propargylic hydroxylamines has been developed. 2,5-Dihydro-4-iodoisoxazole underwent the cross-coupling reactions without aromatization to afford polyfunctionalized 2,5-dihydroisoxazoles. This process was applied to the preparation of valdecoxib and its 2,5-dihydro-derivative.

  DOI：

  10.1021/jo200407b

文献信息

• Alkyne Cycloadditions Mediated by Tetrabutylammonium Fluoride: A Unified and Diversifiable Route to Isoxazolines and Pyrazolines
  作者：Edith Nagy、Salvatore D. Lepore

  DOI：10.1021/acs.orglett.7b01401

  日期：2017.7.21

  isoxazolines and pyrazolines by the cyclization of alkyne substrates using tetrabutylammonium fluoride (TBAF) is described. The reported diheteroatom cycles were produced under mild reaction conditions and with broad product scope. Evidence is also provided for a vinyl anion intermediate produced under unusually mild conditions, which was trapped in situ as part of a tandem cyclization/aldehyde addition sequence

  描述了一种通过使用四丁基氟化铵 (TBAF) 环化炔底物来制备异恶唑啉和吡唑啉的通用方法。报道的二杂原子循环是在温和的反应条件下产生的，并且具有广泛的产物范围。还提供了在异常温和的条件下产生的乙烯基阴离子中间体的证据，该中间体作为串联环化/醛加成序列的一部分被原位捕获。最后，描述了一种脱保护/官能化方法，产生具有良好非对映选择性的取代吡唑啉。
• Design and Synthesis of m1-Selective Muscarinic Agonists:  (<i>R</i>)-(−)-(<i>Z</i>)-1-Azabicyclo[2.2.1]heptan-3-one, <i>O</i>-(3-(3‘-Methoxyphenyl)-2-propynyl)- oxime Maleate (CI<b>-</b>1017), a Functionally m1-Selective Muscarinic Agonist
  作者：Haile Tecle、Stephen D. Barrett、David J. Lauffer、Corinne Augelli-Szafran、Mark R. Brann、Michael J. Callahan、Bradley. W. Caprathe、Robert E. Davis、Patricia D. Doyle、David Eubanks、William Lipiniski、Tara Mirzadegan、Walter H. Moos、D. W. Moreland、Carrie B. Nelson、Michael R. Pavia、Charlotte Raby、Roy D. Schwarz、Carolyn J. Spencer、Anthony J. Thomas、Juan C. Jaen

  DOI：10.1021/jm960683m

  日期：1998.7.1

  The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscarinic agonist. Efficacy and m1 selectivity reside in the R enantiomer, (R)-24Z (CI-1017).

  一系列（Z）-（+/-）-1-氮杂双环[2.2。]的合成和SAR。1]庚烷-3-酮，O-（3-芳基-2-丙炔基）肟被描述。重点介绍了24Z（PD 142505）及其对映异构体的生物化学和药理作用。24Z在功能上是m1选择性毒蕈碱激动剂。功效和m1选择性存在于R对映异构体（R）-24Z（CI-1017）中。
• Synthesis and Biological Characterization of 1,4,5,6-Tetrahydropyrimidine and 2-Amino-3,4,5,6-tetrahydropyridine Derivatives as Selective m1 Agonists
  作者：William S. Messer,、Yahaya F. Abuh、Yang Liu、Sumudra Periyasamy、Dan O. Ngur、Michael A. N. Edgar、Afif A. El-Assadi、Sbeih、Philip G. Dunbar、Scott Roknich、Taikyun Rho、Zheng Fang、Babatunde Ojo、Hao Zhang、James J. Huzl、Peter I. Nagy

  DOI：10.1021/jm960467d

  日期：1997.4.1

  Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Asn382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.