perfluorophenyl 3-(trifluoromethyl)oxetan-3-yl carbonate | 1272974-23-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: perfluorophenyl 3-(trifluoromethyl)oxetan-3-yl carbonate
• 英文别名: carbonic acid pentafluorophenyl ester 3-trifluoromethyl-oxetan-3-yl ester；(2,3,4,5,6-pentafluorophenyl) [3-(trifluoromethyl)oxetan-3-yl] carbonate
• CAS: 1272974-23-8
• 化学式: C₁₁H₄F₈O₄
• 分子量: 352.138
• InChiKey: PAZVAKJZWRWTHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (R)-5-(2-fluoro-4-(methylsulfonyl)benzyloxy)-2-(2-methylpiperazin-1-yl)pyrimidine 、 perfluorophenyl 3-(trifluoromethyl)oxetan-3-yl carbonate 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以67%的产率得到(R)-3-(trifluoromethyl)oxetan-3-yl 4-(5-(2-fluoro-4-(methylsulfonyl)benzyloxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Circumventing Seizure Activity in a Series of G Protein Coupled Receptor 119 (GPR119) Agonists

  摘要：

  Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.

  DOI：

  10.1021/jm5011012
• 作为产物：
  描述：

  双(五氟苯基)碳酸 、 3-(trifluoromethyl)oxetan-3-ol 在 三乙胺 作用下， 以 乙腈 为溶剂， 以84%的产率得到perfluorophenyl 3-(trifluoromethyl)oxetan-3-yl carbonate
  参考文献：
  名称：

  [EN] GPR119 AGONISTS
  [FR] AGONISTES DE GPR119

  摘要：

  本公开至少部分地涉及用于治疗涉及肠脑轴的疾病或疾病的GPR119激动剂。在某些实施例中，GPR119激动剂是肠道限制化合物。在某些实施例中，该疾病或疾病是代谢性疾病，例如糖尿病，肥胖症，非酒精性脂肪性肝炎（NASH）或营养失调，例如短肠综合症。

  公开号：

  WO2022216709A1

文献信息

• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DE TROUBLES LIÉS À CELUI-CI
  申请人：ARENA PHARM INC

  公开号：WO2012145361A1

  公开（公告）日：2012-10-26

  The present invention relates to compounds of Formula I and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及式I的化合物及其药学上可接受的盐、溶剂合物和水合物，这些化合物可作为单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、美格列奈、噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如从以下选择的疾病中选择的疾病：GPR119受体相关疾病；通过增加血液胰高血糖素水平改善的疾病；低骨量症状；神经系统疾病；与代谢相关的疾病；2型糖尿病；肥胖症；以及相关并发症。
• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DE TROUBLES ASSOCIÉS À CELUI-CI
  申请人：ARENA PHARM INC

  公开号：WO2012170702A1

  公开（公告）日：2012-12-13

  The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及具有式(Ia)的化合物以及其药学上可接受的盐、溶剂合物、水合物和N-氧化物，这些化合物可用作单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV的抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、麦格利那类药物、噻唑烷二酮或抗糖尿病肽类似物，在治疗中使用，例如选择自以下疾病的一种：GPR119受体相关疾病；通过增加肠高血糖素分泌改善的情况；通过增加血液高血糖素水平改善的情况；低骨量特征的情况；神经系统疾病；代谢相关疾病；2型糖尿病；肥胖及相关并发症。
• [EN] MODULATORS OF GPR119 AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DE GPR119 ET TRAITEMENT DE TROUBLES ASSOCIÉS À CEUX-CI
  申请人：ARENA PHARM INC

  公开号：WO2014074668A1

  公开（公告）日：2014-05-15

  The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts, solvates, and hydrates thereof, Formula (I), that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, an anti-diabetic peptide analogue, or a DGAT-1 inhibitor, in the treatment of, for example, a disorder selected from: a GPR119-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及化合物的公式(I)及其药学上可接受的盐、溶剂化合物和水合物，公式(I)可作为单一药物代理或与一个或多个其他药物代理结合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、胰岛素分泌促进剂、噻唑烷二酮类药物、抗糖尿病肽类似物或DGAT-1抑制剂，用于治疗例如GPR119相关疾病；通过增加内分泌物分泌改善的疾病；通过增加血液内分泌物水平改善的疾病；低骨量疾病；神经系统疾病；与代谢相关的疾病；2型糖尿病；肥胖及相关并发症。
• Therapeutic Agents 812
  申请人：Birch Alan Martin

  公开号：US20110065706A1

  公开（公告）日：2011-03-17

  A compound of formula I or a pharmaceutically acceptable salt thereof, processes for preparing such compounds, their use as GPR119 modulators, methods for their therapeutic use, particularly in the treatment of obesity and diabetes mellitus, and pharmaceutical compositions containing them.

  公式I的化合物或其药用可接受的盐，制备这类化合物的方法，它们作为GPR119调节剂的用途，它们的治疗用途的方法，特别是在肥胖和糖尿病的治疗中，以及含有它们的药物组合物。
• Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists
  作者：James S. Scott、Alan M. Birch、Katy J. Brocklehurst、Hayley S. Brown、Kristin Goldberg、Sam D. Groombridge、Julian A. Hudson、Andrew G. Leach、Philip A. MacFaul、Darren McKerrecher、Ruth Poultney、Paul Schofield、Per H. Svensson

  DOI：10.1039/c2md20130e

  日期：——

  Improving aqueous solubility is a challenge frequently faced within drug discovery programs. Herein we describe increases in solubility in two sub-series of GPR119 agonists through reduction of lipophilicity together with hydrogen bond acceptor modulation. Small molecule X-ray crystallography was utilised to investigate effects on solid state interactions.

  改善水溶性是药物发现计划中经常面临的挑战。在本文中，我们描述了通过降低亲脂性和氢键受体调节，在两个GPR119激动剂亚系列中增加了溶解度。利用小分子X射线晶体学研究对固态相互作用的影响。