2-(but-2-yn-1-yloxy)isoindoline-1,3-dione | 113211-26-0

• 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-(but-2-yn-1-yloxy)isoindoline-1,3-dione
• 英文别名: 2-But-2-ynyloxy-isoindole-1,3-dione；2-[(But-2-yn-1-yl)oxy]-1H-isoindole-1,3(2H)-dione；2-but-2-ynoxyisoindole-1,3-dione
• CAS: 113211-26-0
• 化学式: C₁₂H₉NO₃
• 分子量: 215.208
• InChiKey: NBMZEQNEQURGME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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-(but-2-yn-1-yloxy)isoindoline-1,3-dione 在 一水合肼 作用下， 反应 0.25h， 生成 O-(but-2-ynyl)hydroxylamine
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of O-Alkynyloximes of Tropinone and N-Methylpiperidinone as Muscarinic Agonists

  摘要：

  A number of O-alkynyloximes of tropinone and N-methyl-4-piperidinone have been synthesized and evaluated for muscarinic activity. The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [H-3]pirenzepine and [H-3]- N-methylscopolamine as radioligands. The oximes bind to the cortical muscarinic receptors with pK(i) values varying from 3 to 7. Higher binding affinities were observed for the O-alkynyl tropinone oximes than the corresponding piperidinone analogues. Binding to the muscarinic sites in the heart and submandibulary glands was also observed but with lower affinities. Good M-1 subtype selectivity (10-fold or greater) was observed with some oximes (26a, 28a, 32a) at the cortical sites. These oximes also attenuated scopolamine-induced impairment of the water mask task in mice. Functional assays for Ma activity on the rat aorta showed that all oximes possessed M-3 agonist action but M-2 agonist activity was not observed at the endothelium-denuded rabbit aorta. Analysis of the quantitative structure-activity relationship (QSAR) indicated that the Connolly surface area is an important determinant of activity, accounting for 70% of the variation in cortical binding affinity among the oximes.

  DOI：

  10.1021/jm9708588
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 2-丁炔-1-醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以3.1 g的产率得到2-(but-2-yn-1-yloxy)isoindoline-1,3-dione
  参考文献：
  名称：

  [EN] AROMATIC AMIDE DERIVATIVE AND USE THEREOF IN ANTITUMOR DRUGS
  [FR] DÉRIVÉ D'AMIDE AROMATIQUE ET SON UTILISATION DANS DES MÉDICAMENTS ANTITUMORAUX
  [ZH] 一种芳香酰胺类衍生物及其在抗肿瘤药物中的应用

  摘要：

  本发明提供一种芳香酰胺类衍生物，其立体异构体，互变异构体，溶剂化物及其药学上可接受的盐，还提供了该类化合物的制备方法以及该类化合物单独的或与其他药物联合使用在预防和/治疗细胞增殖性疾病、特别是与MEK，Raf介导的癌症有关的疾病方面的应用。

  公开号：

  WO2024002210A1

文献信息

• [EN] AROMATIC AMIDE DERIVATIVE AND USE THEREOF IN ANTITUMOR DRUGS<br/>[FR] DÉRIVÉ D'AMIDE AROMATIQUE ET SON UTILISATION DANS DES MÉDICAMENTS ANTITUMORAUX<br/>[ZH] 一种芳香酰胺类衍生物及其在抗肿瘤药物中的应用
  申请人：[en]SHANGHAI ZHEYE BIOTECHNOLOGY CO. LTD.;[zh]上海喆邺生物科技有限公司

  公开号：WO2024002210A1

  公开（公告）日：2024-01-04

  本发明提供一种芳香酰胺类衍生物，其立体异构体，互变异构体，溶剂化物及其药学上可接受的盐，还提供了该类化合物的制备方法以及该类化合物单独的或与其他药物联合使用在预防和/治疗细胞增殖性疾病、特别是与MEK，Raf介导的癌症有关的疾病方面的应用。
• Synthesis and Pharmacological Characterization of <i>O</i>-Alkynyloximes of Tropinone and <i>N</i>-Methylpiperidinone as Muscarinic Agonists
  作者：Rong Xu、Meng-Kwoon Sim、Mei-Lin Go

  DOI：10.1021/jm9708588

  日期：1998.8.1

  A number of O-alkynyloximes of tropinone and N-methyl-4-piperidinone have been synthesized and evaluated for muscarinic activity. The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [H-3]pirenzepine and [H-3]- N-methylscopolamine as radioligands. The oximes bind to the cortical muscarinic receptors with pK(i) values varying from 3 to 7. Higher binding affinities were observed for the O-alkynyl tropinone oximes than the corresponding piperidinone analogues. Binding to the muscarinic sites in the heart and submandibulary glands was also observed but with lower affinities. Good M-1 subtype selectivity (10-fold or greater) was observed with some oximes (26a, 28a, 32a) at the cortical sites. These oximes also attenuated scopolamine-induced impairment of the water mask task in mice. Functional assays for Ma activity on the rat aorta showed that all oximes possessed M-3 agonist action but M-2 agonist activity was not observed at the endothelium-denuded rabbit aorta. Analysis of the quantitative structure-activity relationship (QSAR) indicated that the Connolly surface area is an important determinant of activity, accounting for 70% of the variation in cortical binding affinity among the oximes.
• Design of [<i>R</i>-(<i>Z</i>)]-(+)-α-(Methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitrile (SB 202026), a Functionally Selective Azabicyclic Muscarinic M1 Agonist Incorporating the <i>N</i>-Methoxy Imidoyl Nitrile Group as a Novel Ester Bioisostere
  作者：Steven M. Bromidge、Frank Brown、Frederick Cassidy、Michael S. G. Clark、Steven Dabbs、Michael S. Hadley、Julie Hawkins、Julia M. Loudon、Christopher B. Naylor、Barry S. Orlek、Graham J. Riley

  DOI：10.1021/jm9702903

  日期：1997.12.1

  Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.
• Asymmetric Chiral Ligand-Directed Alkene Dioxygenation
  作者：Sharon R. Neufeldt、Melanie S. Sanford

  DOI：10.1021/ol303003g

  日期：2013.1.4

  A Pd-catalyzed asymmetric alkene 1,2-dioxygenation reaction is described. The diastereoselectivity of the reaction is controlled by tethering a chiral oxime ether directing group to the alkene substrate. The best selectivities are obtained with 8-substituted menthone-derived oxime ether auxiliaries.