methyl 1-[2-fluoro-4-(methylsulfonyl)phenyl]-2-thioxo-3-pyrrolidinecarboxylate | 1001399-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: methyl 1-[2-fluoro-4-(methylsulfonyl)phenyl]-2-thioxo-3-pyrrolidinecarboxylate
• 英文别名: Methyl 1-(2-fluoro-4-methylsulfonylphenyl)-2-sulfanylidenepyrrolidine-3-carboxylate；methyl 1-(2-fluoro-4-methylsulfonylphenyl)-2-sulfanylidenepyrrolidine-3-carboxylate
• CAS: 1001399-55-8
• 化学式: C₁₃H₁₄FNO₄S₂
• 分子量: 331.389
• InChiKey: TUDUWCMQAOXKTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 1-[2-fluoro-4-(methylsulfonyl)phenyl]-2-thioxo-3-pyrrolidinecarboxylate 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 4-chloro-7-[2-fluoro-4-(methylsulfonyl)phenyl]-N-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a
• 作为产物：
  描述：

  5-烯丙基-4,6-二氯嘧啶 在 tetraphosphorus decasulfide 、 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 25.0h， 生成 methyl 1-[2-fluoro-4-(methylsulfonyl)phenyl]-2-thioxo-3-pyrrolidinecarboxylate
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a

文献信息

• WO2008/8895
  申请人：——

  公开号：——

  公开（公告）日：——
• CHEMICAL COMPOUNDS
  申请人：SmithKline Beecham Corporation

  公开号：EP2043744A2

  公开（公告）日：2009-04-08
• US8222261B2
  申请人：——

  公开号：US8222261B2

  公开（公告）日：2012-07-17
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008008887A2

  公开（公告）日：2008-01-17

  [EN] The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly Type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.
  [FR] La présente invention concerne de nouveaux composés utiles pour le traitement de troubles métaboliques, notamment le diabète sucré de type II et les troubles associés, ainsi que des procédés de fabrication et d'utilisation de tels composés.
• [EN] GPR119 AGONISTS FOR THE TREATMENT OF DIABETES AND RELATED DISORDERS<br/>[FR] AGONISTES GPR119 DESTINÉS AU TRAITEMENT DU DIABÈTE ET DES TROUBLES ASSOCIÉS
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008008895A1

  公开（公告）日：2008-01-17

  [EN] The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly Type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.
  [FR] L'invention concerne de nouveaux composés qui sont utiles dans le traitement de troubles métaboliques, en particulier du diabète sucré de type II et des troubles associés, ainsi que les procédés de préparation et d'utilisation desdits composés