methyl 6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-4-carboxylate

• 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 6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-4-carboxylate
• 英文别名: 6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-pyrimidine-4-carboxylate；2-((3aR,6aS)-5-(2-Trifluoromethylphenyl)octahydropyrrolo[3,4-c]pyrrole-2-yl)-6-methylpyrimidine-4-carboxylic acid methyl ester；methyl 2-[(3aS,6aR)-2-[2-(trifluoromethyl)phenyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-6-methylpyrimidine-4-carboxylate
• 化学式: C₂₀H₂₁F₃N₄O₂
• 分子量: 406.408
• InChiKey: ZCCYWMHVJGKRJT-OKILXGFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-4-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以86%的产率得到6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  [EN] OCTAHYDROPYRROLOPYRROLES, THEIR PREPARATION AND USE
  [FR] OCTAHYDROPYRROLOPYRROLES, LEUR PRÉPARATION ET LEUR UTILISATION

  摘要：

  公开号：

  WO2014151936A9
• 作为产物：
  描述：

  邻溴三氟甲苯 在 盐酸 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 22.0h， 生成 methyl 6-methyl-2-((3aR,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-4-carboxylate
  参考文献：
  名称：

  [EN] OCTAHYDROPYRROLOPYRROLES, THEIR PREPARATION AND USE
  [FR] OCTAHYDROPYRROLOPYRROLES, LEUR PRÉPARATION ET LEUR UTILISATION

  摘要：

  公开号：

  WO2014151936A9

文献信息

• OCTAHYDROPYRROLOPYRROLES THEIR PREPARATION AND USE
  申请人：PETRUKHIN Konstantin

  公开号：US20160046632A1

  公开（公告）日：2016-02-18

  The present invention provides compounds comprising variously substituted octahydropyrrolopyrroles, their synthesis, methods of making, methods of using, compositions and formulations thereof.

  本发明提供了包含各种取代的八氢吡咯吡咯化合物，它们的合成方法，制备方法，使用方法，以及它们的组成和配方。
• Octahydropyrrolopyrroles their preparation and use
  申请人：Petrukhin Konstantin

  公开号：US10787453B2

  公开（公告）日：2020-09-29

  The present invention provides compounds comprising variously substituted octahydropyrrolopyrroles, their synthesis, methods of making, methods of using, compositions and formulations thereof.

  本发明提供了包含各种取代的八氢吡咯并吡咯的化合物及其合成、制造方法、使用方法、组合物和制剂。
• US9944644B2
  申请人：——

  公开号：US9944644B2

  公开（公告）日：2018-04-17
• [EN] RBP4 ANTAGONISTS FOR TREATMENT AND PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASE AND GOUT<br/>[FR] ANTAGONISTES DE RBP4 POUR LE TRAITEMENT ET LA PRÉVENTION DE LA STÉATOSE HÉPATIQUE NON ALCOOLIQUE ET DE LA GOUTTE
  申请人：UNIV COLUMBIA

  公开号：WO2020028723A1

  公开（公告）日：2020-02-06

  The subject invention provides a method for treating a non-alcoholic fatty liver disease (NAFLD) disease in a subject afflicted therewith comprising administering to the subject a pharmaceutical composition comprising an amount of a compound which is a non-retinoid retinol- binding protein 4 (RBP4) antagonist effective to treat the subject, thereby treating the subject. The subject invention provides a method for treating gout in a subject afflicted therewith comprising administering to the subject a pharmaceutical composition comprising an amount of a compound which is a retinol-binding protein 4 (RBP4) antagonist effective to treat the subject, thereby treating the subject.
• Bicyclic [3.3.0]-Octahydrocyclopenta[<i>c</i>]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease
  作者：Christopher L. Cioffi、Boglarka Racz、Emily E. Freeman、Michael P. Conlon、Ping Chen、Douglas G. Stafford、Daniel M. C. Schwarz、Lei Zhu、Douglas B. Kitchen、Keith D. Barnes、Nicoleta Dobri、Enrique Michelotti、Charles L. Cywin、William H. Martin、Paul G. Pearson、Graham Johnson、Konstantin Petrukhin

  DOI：10.1021/acs.jmedchem.5b00423

  日期：2015.8.13

  Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AIVID) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant -vision loss associated with geographic atrophy of the macula. We previously disdosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocydopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%).