4-{5-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]pyridin-2-yl}piperazine-1-carboxylic acid ethyl ester | 1085837-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{5-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]pyridin-2-yl}piperazine-1-carboxylic acid ethyl ester
• 英文别名: 4-{5-[(2-Phenyl-5-trifluoromethyloxazole-4-carbonyl)-amino]pyridin-2-yl}piperazine-1-carboxylic Acid Ethyl Ester；ethyl 4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperazine-1-carboxylate
• CAS: 1085837-93-9
• 化学式: C₂₃H₂₂F₃N₅O₄
• 分子量: 489.454
• InChiKey: DFKMQVIVCCQOJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-phenyl-N-[6-piperazin-1-ylpyridin-3-yl]-5-trifluoromethyl-1,3-oxazole-4-carboxamide 、 氯甲酸乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以77%的产率得到4-{5-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]pyridin-2-yl}piperazine-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes

  摘要：

  Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxarnides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 mu M) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, PO, qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT).

  DOI：

  10.1021/jm101580m

文献信息

• Diacylglycerol Acyltransferase Inhibitors
  申请人：Bolin David Robert

  公开号：US20090093497A1

  公开（公告）日：2009-04-09

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

  本文提供的是公式(I)的化合物，以及其药物可接受的盐，其中取代基如规范中所述。这些化合物和含有它们的药物组合物对于治疗疾病，例如肥胖症、2型糖尿病和代谢综合征是有用的。
• INHIBITORS OF DIACYLGLYCEROL ACYLTRANSFERASE
  申请人：Ting Pauline C.

  公开号：US20110224193A1

  公开（公告）日：2011-09-15

  The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase (“DGAT”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown with this abstract.

  本发明涉及一种新型杂环化合物作为二酰基甘油酰基转移酶（“DGAT”）抑制剂，包括所述杂环化合物的制药组合物以及使用所述化合物治疗或预防心血管疾病、代谢紊乱、肥胖或肥胖相关疾病、糖尿病、血脂异常、糖尿病并发症、糖耐量受损或空腹血糖受损。本发明的一种示例化合物如本摘要所示。
• DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS
  申请人：Via Pharmaceuticals, Inc.

  公开号：EP2155687A1

  公开（公告）日：2010-02-24
• US8058299B2
  申请人：——

  公开号：US8058299B2

  公开（公告）日：2011-11-15
• US8115011B2
  申请人：——

  公开号：US8115011B2

  公开（公告）日：2012-02-14