1-[3-methyl-7-(3-methyl-but-2-enyl)-2,6-dioxo-1-(2-oxo-2-phenyl-ethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]-cis-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3-methyl-7-(3-methyl-but-2-enyl)-2,6-dioxo-1-(2-oxo-2-phenyl-ethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]-cis-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 1-[3-methyl-7-(3-methylbut-2-enyl)-2,6-dioxo-1-phenacylpurin-8-yl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carboxylate
• 化学式: C₃₀H₃₈N₆O₅
• 分子量: 562.669
• InChiKey: VSWVZMUFHPKNEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[3-methyl-7-(3-methyl-but-2-enyl)-2,6-dioxo-1-(2-oxo-2-phenyl-ethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]-cis-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester 在 甲烷磺酸 作用下， 以 N-甲基吡咯烷酮 、 水 为溶剂， 生成 8-(3,3a,4,5,6,6a-hexahydro-2H-pyrrolo[2,3-c]pyrrol-1-yl)-3-methyl-7-(3-methylbut-2-enyl)-1-phenacylpurine-2,6-dione
  参考文献：
  名称：

  Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery

  摘要：

  A novel integrated discovery platform has been used to synthesize and biologically assay a series of xanthine-derived dipeptidyl peptidase 4 (DPP4) antagonists. Design, synthesis, purification, quantitation, dilution, and bioassay have all been fully integrated to allow continuous automated operation. The system has been validated against a set of known DPP4 inhibitors and shown to give excellent correlation between traditional medicinal chemistry generated biological data and platform data. Each iterative loop of synthesis through biological assay took two hours in total, demonstrating rapid iterative structure-activity relationship generation.

  DOI：

  10.1021/ml400171b
• 作为产物：
  描述：

  8-bromo-3-methyl-7-(3-methyl-but-2-enyl)-1-(2-oxo-2-phenyl-ethyl)-3,7-dihydro-purine-2,6-dione 、 六氢吡咯并[3,4-b]吡咯-5-羧酸叔丁酯 在 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 6.0h， 生成 1-[3-methyl-7-(3-methyl-but-2-enyl)-2,6-dioxo-1-(2-oxo-2-phenyl-ethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]-cis-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [DE] SUBSTITUIERTE, BIZYKLISCHE 8-PYRROLIDINO-XANTHINE UND IHRE VERWENDUNG ALS INHIBITOREN DER DIPEPTIDYL PEPTIDASE IV
  [EN] SUBSTITUTED BICYCLIC 8-PYRROLIDINO-XANTHINES AND USE THEREOF AS INHIBITORS OF THE DIPEPTIDYL PEPTIDASE IV
  [FR] 8-PYRROLIDINO-XANTHINES BICYCLIQUES SUBSTITUEES ET LEUR UTILISATION COMME INHIBITEURS DE LA DIPEPTIDYLPEPTIDASE IV

  摘要：

  这项发明涉及取代的双环8-吡咯啉基黄嘌呤以及其生理相容盐和生理功能衍生物。该发明涉及式(I)的化合物，其中残基具有所述的含义，以及它们的生理相容盐。这些化合物可用作预防和治疗2型糖尿病的药物。

  公开号：

  WO2006015699A1

文献信息

• [DE] SUBSTITUIERTE, BIZYKLISCHE 8-PYRROLIDINO-XANTHINE UND IHRE VERWENDUNG ALS INHIBITOREN DER DIPEPTIDYL PEPTIDASE IV<br/>[EN] SUBSTITUTED BICYCLIC 8-PYRROLIDINO-XANTHINES AND USE THEREOF AS INHIBITORS OF THE DIPEPTIDYL PEPTIDASE IV<br/>[FR] 8-PYRROLIDINO-XANTHINES BICYCLIQUES SUBSTITUEES ET LEUR UTILISATION COMME INHIBITEURS DE LA DIPEPTIDYLPEPTIDASE IV
  申请人：SANOFI AVENTIS DEUTSCHLAND

  公开号：WO2006015699A1

  公开（公告）日：2006-02-16

  Die Erfindung betrifft substituierte, bizyklische 8-Pyrrolidino-xanthine sowie deren physiologisch verträgliche Salze und physiologisch funktionelle Derivate. Die Erfindung betrifft Verbindungen der Formel (I), worin die Reste die angegebenen Bedeutungen haben, sowie deren physiologisch verträgliche Salze. Die Verbindungen eignen sich z.B. als Medikamente zur Prävention und Behandlung von Diabetes Typ 2.

  这项发明涉及取代的双环8-吡咯啉基黄嘌呤以及其生理相容盐和生理功能衍生物。该发明涉及式(I)的化合物，其中残基具有所述的含义，以及它们的生理相容盐。这些化合物可用作预防和治疗2型糖尿病的药物。
• SUBSTITUTED, BICYCLIC 8-PYRROLIDINOXANTHINES, AND METHODS FOR THEIR USE AS INHIBITORS OF DIPEPTIDYL PEPTIDASE
  申请人：SCHOENAFINGER Karl

  公开号：US20070197563A1

  公开（公告）日：2007-08-23

  The present invention involves substituted bicyclic 8-pyrrolidinoxanthines and their derivatives of formula I: wherein the various R groups are defined herein. The present invention also comprises pharmaceutical compositions comprising them as well as processes for the preparation of these compounds and methods for the treatment of metabolic disorders such as type-2 diabetes, insulin resistance, hyperglycemia, arteriosclerosis diseases and the like through the administration of said compositions.

  本发明涉及替代的双环8-吡咯啉二氧嘌呤及其衍生物的化合物，其化学式为I：其中各个R基在此处定义。本发明还包括含有这些化合物的药物组合物，以及用于制备这些化合物的方法和通过给予所述组合物来治疗代谢性疾病，如2型糖尿病、胰岛素抵抗、高血糖、动脉硬化疾病等的方法。
• US7888343B2
  申请人：——

  公开号：US7888343B2

  公开（公告）日：2011-02-15
• Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery
  作者：Werngard Czechtizky、Jüergen Dedio、Bimbisar Desai、Karen Dixon、Elizabeth Farrant、Qixing Feng、Trevor Morgan、David M. Parry、Manoj K. Ramjee、Christopher N. Selway、Thorsten Schmidt、Gary J. Tarver、Adrian G. Wright

  DOI：10.1021/ml400171b

  日期：2013.8.8

  A novel integrated discovery platform has been used to synthesize and biologically assay a series of xanthine-derived dipeptidyl peptidase 4 (DPP4) antagonists. Design, synthesis, purification, quantitation, dilution, and bioassay have all been fully integrated to allow continuous automated operation. The system has been validated against a set of known DPP4 inhibitors and shown to give excellent correlation between traditional medicinal chemistry generated biological data and platform data. Each iterative loop of synthesis through biological assay took two hours in total, demonstrating rapid iterative structure-activity relationship generation.