methyl (2-(1-methoxymethyl)-2-(phenylthio)imidazol-5-yl)glyoxylate | 219817-91-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: methyl (2-(1-methoxymethyl)-2-(phenylthio)imidazol-5-yl)glyoxylate
• 英文别名: Methyl 2-(1-methoxymethyl-2phenylthioimidazol-5yl)glyoxylate；Methyl 2-[3-(methoxymethyl)-2-(phenylsulfanyl)imidazol-4-yl]-2-oxoacetate；methyl 2-[3-(methoxymethyl)-2-phenylsulfanylimidazol-4-yl]-2-oxoacetate
• CAS: 219817-91-1
• 化学式: C₁₄H₁₄N₂O₄S
• 分子量: 306.342
• InChiKey: PQMMUFQOLMXFPM-UHFFFAOYSA-N

物化性质

• 沸点：
  479.9±51.0 °C(predicted)
• 密度：
  1.29±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  95.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2-(1-methoxymethyl)-2-(phenylthio)imidazol-5-yl)glyoxylate 在 4 A molecular sieve 、 potassium tert-butylate 、 三溴化硼 、 镍 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 didemnimide A
  参考文献：
  名称：

  Granulatimide and Isogranulatimide, Aromatic Alkaloids with G2 Checkpoint Inhibition Activity Isolated from the Brazilian Ascidian Didemnum granulatum:  Structure Elucidation and Synthesis

  摘要：

  Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.

  DOI：

  10.1021/jo981607p
• 作为产物：
  描述：

  草酸二甲酯 、 1-(methoxymethyl)-2-(phenylthio)-1H-imidazole 在 正丁基锂 作用下， 生成 methyl (2-(1-methoxymethyl)-2-(phenylthio)imidazol-5-yl)glyoxylate
  参考文献：
  名称：

  Granulatimide and Isogranulatimide, Aromatic Alkaloids with G2 Checkpoint Inhibition Activity Isolated from the Brazilian Ascidian Didemnum granulatum:  Structure Elucidation and Synthesis

  摘要：

  Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.

  DOI：

  10.1021/jo981607p

文献信息

• Granulatimide compounds and uses thereof
  申请人：The University of British Columbia

  公开号：US06291447B1

  公开（公告）日：2001-09-18

  Novel granulatimide compounds and pharmaceutical formulations thereof are provided. Compounds of this invention have the general formula: wherein are independently R or Z as defined below, or in combination F and F′ is Ar1 as defined below; Ar1 is a monocyclic, bicyclic or tricyclic, fully or partially aromatic system containing five or six membered carbocyclic or, oxygen, nitrogen or sulphur containing heterocyclic rings, optionally substituted with R or Z; W is selected from the group consisting of formula (i); (ii) or (iii), wherein the structures are as follows:

  本发明提供了新型的颗粒状酰胺化合物及其制药组合物。该发明的化合物具有以下通式：其中R或Z独立地定义如下，或者F和F'的组合是以下定义的Ar1；Ar1是一个含有五个或六个成员的碳环或含氧、氮或硫杂环的单环、双环或三环、完全或部分芳香性系统，可选地取代R或Z；W从以下公式（i）、（ii）或（iii）的群组中选取，结构如下：
• GRANULATIMIDE DERIVATIVES FOR USE IN CANCER TREATMENT
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：EP1070068A1

  公开（公告）日：2001-01-24
• US6291447B1
  申请人：——

  公开号：US6291447B1

  公开（公告）日：2001-09-18
• [EN] GRANULATIMIDE DERIVATIVES FOR USE IN CANCER TREATMENT<br/>[FR] DERIVES DE GRANULATIMIDE UTILISES DANS LE TRAITEMENT DU CANCER
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：WO1999047522A1

  公开（公告）日：1999-09-23

  (EN) Novel granulatimide compounds and pharmaceutical formulations thereof are provided. Compounds of this invention have general formula (I) or (II) wherein are independently R or Z as defined below, or in combination F and F' is Ar1 as defined below; Ar1 is a monocyclic, bicyclic or tricyclic, fully or partially aromatic system containing five or six membered carbocyclic or, oxygen, nitrogen or sulphur containing heterocyclic rings, optionally substituted with R or Z; W is selected from the group consisting of formula (i); (ii) or (iii), wherein the structures are as described in: (i), (ii) and (iii). R and Z are optional substituents as defined in the application.(FR) L'invention concerne de nouveaux composés de granulatimide et des formulations pharmaceutiques de ceux-ci. Les composés de l'invention sont représentés par la formule (I) ou (II). Dans cette formule, F et F' représentent indépendamment R ou Z tels que définis ci-dessous, ou F et F' en combinaison représentent Ar1 tel que défini ci-dessous; Ar1 représente un système monocyclique, bicyclique ou tricyclique partiellement ou totalement aromatique, contenant des noyaux carbocycliques à cinq ou six éléments, ou de l'oxygène, de l'azote ou du soufre comprenant des noyaux hétérocycliques, éventuellement substitués par R ou Z; W est sélectionné dans le groupe constitué par les formules (i), (ii) ou (iii), les structures étant telles que ci-dessous.
• Granulatimide and Isogranulatimide, Aromatic Alkaloids with G2 Checkpoint Inhibition Activity Isolated from the Brazilian Ascidian <i>Didemnum </i><i>granulatum</i>:  Structure Elucidation and Synthesis
  作者：Roberto G. S. Berlinck、Robert Britton、Edward Piers、Lynette Lim、Michel Roberge、Rosana Moreira da Rocha、Raymond J. Andersen

  DOI：10.1021/jo981607p

  日期：1998.12.1

  Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.