methyl (5-methyl-1-phenylpyrazol-3-yl)acetate | 289054-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl (5-methyl-1-phenylpyrazol-3-yl)acetate
• 英文别名: (5-methyl-1-phenyl-1H-pyrazol-3-yl)-acetic acid methyl ester；(5-Methyl-1-phenyl-1H-pyrazol-3-yl)-essigsaeure-methylester；Methyl 2-(5-methyl-1-phenylpyrazol-3-yl)acetate
• CAS: 289054-51-9
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: CFIIPLBVWDQVNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (5-methyl-1-phenylpyrazol-3-yl)acetate 在 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 2(S)-<(2-benzoylphenyl)amino>-3-<4-<2-(5-methyl-1-phenyl-1H-pyrazol-3-yl)ethoxy>phenyl>propionic acid methyl ester
  参考文献：
  名称：

  N-(2-Benzoylphenyl)-l-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety

  摘要：

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-{2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.

  DOI：

  10.1021/jm980413z
• 作为产物：
  描述：

  重氮甲烷 、 1-phenyl-5-methyl-1H-pyrazole-3-carbonyl chloride 在 乙醚 作用下， 生成 methyl (5-methyl-1-phenylpyrazol-3-yl)acetate
  参考文献：
  名称：

  Differences in Wage Distributions Between Canada and the United States: An Application of a Flexible Estimator of Distribution Functions in the Presence of Covariates

  摘要：

  We construct a tractable, flexible-functional-form estimator of cumulative distribution functions for non-negative random variables which admits large numbers of covariates. The estimator adopts and extends techniques from the spell-duration literature for estimating hazard functions to distribution functions for wages, earnings, and income. We apply these methods to investigate sources of wage inequality for full-time male workers between Canada and the United States, finding that the Canadian wage density has a thinner left tail because low-educated workers have higher pay and a thinner right tail because of a lower proportion of highly-educated workers. Unions appear to play a large role in these outcomes.

  DOI：

  10.1111/1467-937x.00147

文献信息

• Synthesis of Esters from Olefins, Hydrogen, Carbon Monoxide and Acetic Acid
  作者：Ralph C. Schreyer

  DOI：10.1021/ja01133a012

  日期：1952.7
• Chemoselective Synthesis of 3- and 5-Pyrazolylacetates
  作者：Augusto C. Veronese、Chiara B. Vicentini、Maurizio Manfrini、Manuela Mazzanti、Monica Manferdini、Carlo F. Morelli

  DOI：10.3987/com-00-8871

  日期：——