methanesulfonic acid 2-(5-methyl-2-p-tolyloxazol-4-yl)ethyl ester | 477541-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methanesulfonic acid 2-(5-methyl-2-p-tolyloxazol-4-yl)ethyl ester
• 英文别名: 2-[5-methyl-2-(p-tolyl)oxazol-4-yl]ethyl methanesulfonate；2-[5-Methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]ethyl methanesulfonate
• CAS: 477541-32-5
• 化学式: C₁₄H₁₇NO₄S
• 分子量: 295.359
• InChiKey: QTRKACOCIYXNHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  77.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 2-(5-methyl-2-p-tolyloxazol-4-yl)ethyl ester 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 24.0h， 生成 3-{2-ethyl-4-[2-(5-methyl-2-p-tolyloxazol-4-yl)ethoxy]phenyl}propanoic acid
  参考文献：
  名称：

  Design and Synthesis of 3-(2-Ethyl-4-{2-[2-(4-fluorophenyl)-5-methyloxazol-4-yl]ethoxy}phenyl)propanoic Acid: A Novel Triple-acting PPARα, -γ, and -δ Agonist

  摘要：

  本文描述了三重作用PPARα、-γ和-δ激动剂3-(2-乙基-4-{2-[2-(4-氟苯基)-5-甲基噁唑-4-基]乙氧基}苯基)丙酸(1a)的设计与合成。该化合物具有强大的三重作用PPARα、-γ和-δ激动剂特性，其EC50值分别为0.029、0.013和0.029 µM。合成路线以噁唑环的合成为关键步骤，从市售的3-氧代戊酸甲酯和3-羟基苯乙酮出发，最终得到目标化合物1，总产率为32%。

  DOI：

  10.1246/cl.2012.406
• 作为产物：
  描述：

  5-羟基-2-戊酮 在 吡啶 、 盐酸 、 sodium azide 、 palladium on activated charcoal 、 氢气 、 溴 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 丙酮 、 甲苯 为溶剂， 反应 125.0h， 生成 methanesulfonic acid 2-(5-methyl-2-p-tolyloxazol-4-yl)ethyl ester
  参考文献：
  名称：

  Design and Synthesis of 3-(2-Ethyl-4-{2-[2-(4-fluorophenyl)-5-methyloxazol-4-yl]ethoxy}phenyl)propanoic Acid: A Novel Triple-acting PPARα, -γ, and -δ Agonist

  摘要：

  本文描述了三重作用PPARα、-γ和-δ激动剂3-(2-乙基-4-{2-[2-(4-氟苯基)-5-甲基噁唑-4-基]乙氧基}苯基)丙酸(1a)的设计与合成。该化合物具有强大的三重作用PPARα、-γ和-δ激动剂特性，其EC50值分别为0.029、0.013和0.029 µM。合成路线以噁唑环的合成为关键步骤，从市售的3-氧代戊酸甲酯和3-羟基苯乙酮出发，最终得到目标化合物1，总产率为32%。

  DOI：

  10.1246/cl.2012.406

文献信息

• Design and synthesis of novel oxazole containing 1,3-Dioxane-2-carboxylic acid derivatives as PPAR α/γ dual agonists
  作者：Harikishore Pingali、Mukul Jain、Shailesh Shah、Pankaj Makadia、Pandurang Zaware、Ashish Goel、Megha Patel、Suresh Giri、Harilal Patel、Pankaj Patel

  DOI：10.1016/j.bmc.2008.06.050

  日期：2008.8

  A few novel 1,3-dioxane carboxylic acid derivatives were designed and synthesized to aid in the characterization of PPAR alpha/gamma dual agonists. Structural requirements for PPARalpha/gamma dual agonism of 1,3-dioxane carboxylic acid derivatives included the structural similarity with potent glitazones in fibric acid chemotype. The compounds with this pharmacophore and substituted oxazole as a lipophilic

  设计和合成了一些新颖的1,3-二恶烷羧酸衍生物，以帮助表征PPARα/γ双激动剂。1,3-二恶烷羧酸衍生物的PPARalpha /γ双激动性的结构要求包括与强酸格列酮在纤维酸化学型中的结构相似性。合成了具有该药效团和取代的恶唑作为亲脂性杂环尾巴的化合物，并在动物模型中评估了其体外PPAR激动剂的潜力以及体内降血糖和降血脂的功效。铅化合物2-甲基-c-5- [4-（5-（甲基-2-（4-甲基苯基）-恶唑-4-基甲氧基）-苄基] -1,3-二恶烷-r-2-羧酸13b在db / db小鼠和Zucker fa / fa大鼠中表现出有效的降血糖，降血脂和胰岛素增敏作用。
• Novel heterocyclic derivatives and medicinal use thereof
  申请人：——

  公开号：US20040180924A1

  公开（公告）日：2004-09-16

  The novel heterocyclic derivative of the present invention is a novel heterocyclic derivative having the formula (I′) 1 wherein R 1 is a hydrogen atom or C 1-6 alkyl, R 2 is —CO—C(R 4 )═C(R 4 )—R 5 wherein R 4 is a hydrogen atom or C 1-4 alkyl, and R 5 is C 4-8 alkyl, C 2-8 alkenyl, aryl or aromatic heterocycle, —CO—C≡C—R 6 wherein R 6 is C 1-8 alkyl and the like, R 3 is a hydrogen atom or C 1-4 alkyl, X is an oxygen atom or a sulfur atom, R 20 is optionally substituted phenyl, and n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof. The compound (I′) of the present invention is useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complications, a glucose tolerance improver, an anti-arteriosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated diseases and an agent for the prophylaxis or treatment of syndrome X.

  本发明的新型杂环衍生物是一种具有公式（I'）的新型杂环衍生物，其中R1是氢原子或C1-6烷基，R2是—CO—C(R4)═C(R4)—R5，其中R4是氢原子或C1-4烷基，R5是C4-8烷基、C2-8烯基、芳香族或芳香族杂环，—CO—C≡C—R6，其中R6是C1-8烷基等，R3是氢原子或C1-4烷基，X是氧原子或硫原子，R20是可选取代的苯基，n是1到4的整数，或其药学上可接受的盐。本发明的化合物（I'）可用作降血糖剂、降血脂剂、胰岛素抵抗改善剂、糖尿病治疗剂、糖尿病并发症治疗剂、葡萄糖耐量改善剂、抗动脉硬化剂、抗肥胖剂、抗炎剂、预防或治疗PPAR介导的疾病的药剂和预防或治疗X综合征的药剂。
• NOVEL HETEROCYCLIC DERIVATIVES AND MEDICINAL USE THEREOF
  申请人：Kyoto Pharmaceutical Industries, Ltd.

  公开号：EP1398313A1

  公开（公告）日：2004-03-17

  The novel heterocyclic derivative of the present invention is a novel heterocyclic derivative having the formula (I') wherein R1 is a hydrogen atom or C1-6 alkyl, R2 is -CO-C(R4)=C(R4)-R5 wherein R4 is a hydrogen atom or C1-4 alkyl, and R5 is C4-8 alkyl, C2-8 alkenyl, aryl or aromatic heterocycle, -CO-C≡C-R6 wherein R6 is C1-8 alkyl and the like, R3 is a hydrogen atom or C1-4 alkyl, X is an oxygen atom or a sulfur atom, R20 is optionally substituted phenyl, and n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof. The compound (I') of the present invention is useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complications, a glucose tolerance improver, an anti-arteriosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated diseases and an agent for the prophylaxis or treatment of syndrome X.

  本发明的新型杂环衍生物是具有式（I'）的新型杂环衍生物 其中 R1 是氢原子或 C1-6 烷基，R2 是 -CO-C(R4)=C(R4)-R5 其中 R4 是氢原子或 C1-4 烷基，R5 是 C4-8 烷基、C2-8 烯基、芳基或芳香杂环，-CO-C≡C-R6 其中 R6 是 C1-8 烷基等，R3 是氢原子或 C1-4 烷基，X 是氧原子或硫原子，R20 是任选取代的苯基，n 是 1 至 4 的整数，或其药学上可接受的盐。本发明的化合物（I'）可用作降血糖剂、降血脂剂、胰岛素抵抗改善剂、糖尿病治疗剂、糖尿病并发症治疗剂、葡萄糖耐量改善剂、抗动脉硬化剂、抗肥胖剂、抗炎剂、预防或治疗 PPAR 介导的疾病的药物以及预防或治疗 X 综合征的药物。
• Modulation of PPAR receptor subtype selectivity of the ligands: Aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety
  作者：Harikishore Pingali、Mukul Jain、Shailesh Shah、Pravin Patil、Pankaj Makadia、Pandurang Zaware、Kalapatapu V.V.M. Sairam、Jeevankumar Jamili、Ashish Goel、Megha Patel、Pankaj Patel

  DOI：10.1016/j.bmcl.2008.10.062

  日期：2008.12

  Oxazole containing glycine and oximinobutyric acid derivatives were synthesized as PPAR alpha agonists by incorporating polymethylene spacer as a replacement of commonly used phenylene group that connects the acidic head with lipophilic tail. Compound 13a was found to be a selective and potent PPAR alpha agonist. Further 1,3-dioxane-2-carboxylic acid derivative 20 was synthesized by replacing the tetramethylene spacer of NS-220, a selective PPAR alpha agonist with phenylene group and found to exhibit PPAR alpha/gamma dual agonism. These results suggest that compounds possessing polymethylene spacer between pharmacophore and lipophilic tail exhibit predominantly PPARa agonism whereas those with an aromatic phenylene spacer shows PPAR alpha/gamma dual agonism. (C) 2008 Elsevier Ltd. All rights reserved.
• WO2008/117982
  申请人：——

  公开号：——

  公开（公告）日：——