2-[2-(4-methoxybenzyl)-3-oxoisoindolin-1-yl]acetic acid | 935686-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-[2-(4-methoxybenzyl)-3-oxoisoindolin-1-yl]acetic acid
• 英文别名: [2-(4-Methoxy-benzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-acetic acid；2-[2-[(4-methoxyphenyl)methyl]-3-oxo-1H-isoindol-1-yl]acetic acid
• CAS: 935686-82-1
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: KCYSLUHSUOPEJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[2-(4-methoxybenzyl)-3-oxoisoindolin-1-yl]acetic acid 在 草酰氯 、 silver trifluoroacetate 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.0h， 生成 3-[2-(4-methoxybenzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-propionic acid
  参考文献：
  名称：

  General Approach to Nitrogen-Bridged Bicyclic Frameworks by Rh-Catalyzed Formal Carbenoid Insertion into an Amide C–N Bond

  摘要：

  Various nitrogen-bridged bicyclic skeletons are found in bioactive natural products and pharmaceuticals. The development of a new reaction to construct these molecular frameworks has attracted considerable attention in synthetic organic chemistry. We developed a novel synthetic method for obtaining a wide variety of nitrogen-bridged bicyclic compounds with a catalytic process, Rh-catalyzed formal carbenoid insertion into an amide C-N bond. Using 0.1-0.4 mol % Rh-2((NHCOBu)-Bu-t)(4) catalyst, various azabicydo[X.Y.Z]alkane derivatives were obtained in good to excellent yield, successfully demonstrating the broad substrate scope of the developed process. Experimental and computational studies to elucidate the reaction mechanism revealed that the formal insertion reaction of a carbenoid into an amide C-N bond proceeded via the formation of Rh-associated N-ylides, followed by an acyl group-selective Stevens [1,2]-shift through a concerted addition/elimination process on the sp(2)-hybridized carbon.

  DOI：

  10.1021/acs.joc.5b01954
• 作为产物：
  描述：

  2-[(4-methoxyphenyl)methyl]-1H-isoindole-1,3(2H)-dione 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 56.0h， 生成 2-[2-(4-methoxybenzyl)-3-oxoisoindolin-1-yl]acetic acid
  参考文献：
  名称：

  [EN] TRICYCLIC GPR65 MODULATORS
  [FR] MODULATEURS TRICYCLIQUES DE LA GPR65

  摘要：

  One aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, (I) wherein: ring B is: a monocyclic aromatic group; or a monocyclic or bicyclic heteroaromatic group, each of which is optionally substituted by halo, CN, OH, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, O-cycloalkyl, alkoxy, haloalkoxy, heterocycloalkyl, O- heterocycloalkyl, aryl, heteroaryl, O-aryl, NHCO-alkenyl, NHCO-aryl, -(CH2)q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and CO2-alkyl, wherein said aryl, heteroaryl, heterocycloalkyl, O-cycloalkyl, NHCO-aryl, -(CH2)q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and O-aryl groups are each optionally further substituted by one or more groups independently selected from halo, alkyl, haloalkyl, alkoxy, NHCO-alkyl, NR13R13', SO2-alkyl, CN, hydroxyalkyl, CONR14R14', alkyl-NR15R15', heterocycloalkyl, alkyl-heterocycloalkyl, alkyl- cycloalkyl, aryl, (CH2)m-NHSO2-alkyl, CO2R16, alkoxy-alkyl, haloalkoxy, O-heterocycloalkyl, heteroaryl, alkoxy-alkoxy, and O-(CH2)p-cycloalkyl, where in the latter group, said cycloalkyl group is optionally further substituted by one or more halo, haloalkyl, alkyl or alkoxy groups; m is an integer from 0 to 3; p and q are each independently 0 to 3; Z is CR12; Y is CR10R10', wherein R10and R10'are each independently selected from H, F, alkyl, and haloalkyl; Raand Rbare each independently selected from H and alkyl; R6is selected from H, alkyl, cycloalkyl and hydroxyalkyl; R12is selected from H, alkyl, haloalkyl, halo, OH and O-alkyl; and R13, R13', R14, R14', R15, R15', and R16are each independently selected from H, alkyl, and alkoxyalkyl. Further aspects of the invention relate to compounds of formula (I) for use as a medicament, particularly in the field of immuno-oncology, immunology, and related applications.

  公开号：

  WO2023067322A1

文献信息

• Substituted Dihydroisoindolones As Allosteric Modulators of Glucokinase
  申请人：Dudash Joseph

  公开号：US20070099930A1

  公开（公告）日：2007-05-03

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating glucokinase mediated disorders. More particularly, the compounds of the present invention are glucokinase modulators useful for treating disorders including, but not limited to, type II diabetes.

  本发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体和衍生物，以及用于治疗葡萄糖激酶介导的疾病。更具体地说，本发明的化合物是葡萄糖激酶调节剂，可用于治疗包括但不限于II型糖尿病在内的疾病。
• Substituted dihydroisoindolones as allosteric modulators of glucokinase
  申请人：Dudash Joseph

  公开号：US08796313B2

  公开（公告）日：2014-08-05

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating glucokinase mediated disorders. More particularly, the compounds of the present invention are glucokinase modulators useful for treating disorders including, but not limited to, type II diabetes.

  本发明涉及公式（I）的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗葡萄糖激酶介导的疾病。更具体地说，本发明的化合物是葡萄糖激酶调节剂，可用于治疗包括但不限于II型糖尿病在内的疾病。
• SUBSTITUTED DIHYDROISOINDOLONES AS ALLOSTERIC MODULATORS OF GLUCOKINASE
  申请人：Janssen Pharmaceutica NV

  公开号：EP1960385A1

  公开（公告）日：2008-08-27
• US8796313B2
  申请人：——

  公开号：US8796313B2

  公开（公告）日：2014-08-05
• [EN] SUBSTITUTED DIHYDROISOINDOLONES AS ALLOSTERIC MODULATORS OF GLUCOKINASE<br/>[FR] DIHYDROISOINDOLONES SUBSTITUTÉES MODULATEURS UTILISÉES EN TANT QUE ALLOSTÉRIQUES DE LA GLUCOKINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2007053503A1

  公开（公告）日：2007-05-10

  [EN] The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating glucokinase mediated disorders. More particularly, the compounds of the present invention are glucokinase modulators useful for treating disorders including, but not limited to, type II diabetes.
  [FR] La présente invention concerne des composés de formule (I), des méthodes pour préparer lesdits composés, des compositions, des intermédiaires et des dérivés de ceux-ci, et pour traiter des troubles médiés par la glucokinase. Plus particulièrement, les composés de la présente invention sont des modulateurs de la glucokinase utiles pour traiter des troubles y compris, mais sans s'y limiter, le diabète de type II.