(2-oxo-3-m-tolylpropyl)phosphonic acid dimethyl ester | 61263-05-6

• 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: (2-oxo-3-m-tolylpropyl)phosphonic acid dimethyl ester
• 英文别名: dimethyl [3-(3-methylphenyl)-2-oxopropane]phosphonate；Phosphonic acid, [3-(3-methylphenyl)-2-oxopropyl]-, dimethyl ester；1-dimethoxyphosphoryl-3-(3-methylphenyl)propan-2-one
• CAS: 61263-05-6
• 化学式: C₁₂H₁₇O₄P
• 分子量: 256.238
• InChiKey: QDYNKFNOVKBWCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-oxo-3-m-tolylpropyl)phosphonic acid dimethyl ester 在 sodium tetrahydroborate 、 cerium(III) chloride 、 sodium hydride 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 生成 (15S)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin methylester
  参考文献：
  名称：

  Suzuki, Masaaki; Kato, Koichi; Noyori, Ryoji, Angewandte Chemie, 1996, vol. 108, # 3, p. 366 - 369

  摘要：

  DOI：
• 作为产物：
  描述：

  3-甲基苯乙酸 在 正丁基锂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 正己烷 、 甲苯 、 乙腈 为溶剂， 反应 4.0h， 生成 (2-oxo-3-m-tolylpropyl)phosphonic acid dimethyl ester
  参考文献：
  名称：

  Discovery of Orally Available 8-Aza-5-thiaProstaglandin E1 Analogs as Highly Selective EP4 Agonists

  摘要：

  合成了 8-aza-16-aryl 前列腺素 E1 (PGE1) 和 8-aza-5-thia-16-arylPGE1 类似物，并对它们的亚型受体亲和力和 EP4 激动剂活性进行了评估，以确定具有口服疗效的亚型选择性 EP4 激动剂。通过抑制大鼠体内脂多糖（LPS）诱导的肿瘤坏死因子（TNF）-α的产生，对代表性化合物的药代动力学特征和体内疗效进行了评估。对结构-活性关系（SARs）进行了表征和展示。与之前报道的类似物 2a 相比，在测试的化合物中，有几种显示出更好的口服暴露和/或体内疗效。

  DOI：

  10.1248/cpb.59.1523

文献信息

• A Convenient Procedure for the Synthesis of 2,2,2-Trifluoroethyl Methyl 2-Oxoalkylphosphonates
  作者：Katalin Molnár、Julien Behra、László Takács、Mihály Kádár、Zsuzsanna Kardos、Ferenc Faigl

  DOI：10.1080/10426507.2014.978326

  日期：2015.6.3

  convenient and versatile method was developed for the synthesis of 2,2,2-trifluoroethyl methyl 2-oxoalkylphosphonates starting from dimethyl phosphonates by alkaline hydrolysis followed by esterification with 2,2,2-trifluoroethanol using diisopropylcarbodiimide (DIC) in the presence of 4-(dimethylamino)pyridine (DMAP) catalyst following the Steglich protocol.

  图形摘要 摘要 开发了一种方便且通用的方法，从膦酸二甲酯开始，通过碱水解，然后使用二异丙基碳二亚胺 (DIC) 与 2,2,2-三氟乙醇酯化合成 2,2,2-三氟乙基甲基 2-氧代烷基膦酸酯。遵循 Steglich 方案，存在 4-（二甲氨基）吡啶（DMAP）催化剂。
• Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hideyuki Yoshida、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.02.018

  日期：2012.4

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of a novel EP2/EP4 dual agonist with high subtype-selectivity
  作者：Tohru Kambe、Toru Maruyama、Masayuki Nakano、Yoshihiko Nakai、Tadahiro Yoshida、Naoki Matsunaga、Hiroji Oida、Akira Konaka、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmcl.2011.10.109

  日期：2012.1

  A series of gamma-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the omega-chain and aryl moiety in the alpha-chain were synthesized and biologically evaluated. Among the tested compounds, gamma-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2 = 9.3 nM, mEP4 = 0.41 nM). A structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of novel modified γ-lactam prostanoids as EP4 subtype-selective agonists
  作者：Tohru Kambe、Toru Maruyama、Toshihiko Nagase、Seiji Ogawa、Chiaki Minamoto、Kiyoto Sakata、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2011.12.009

  日期：2012.1

  To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified gamma-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the gamma-hydroxycyclopentanone without a troublesome 11-hydroxy group were identified as highly subtype-selective EP4 agonists. Among the tested, several representative compounds demonstrated in vivo efficacy after oral dosing in rats. Their pharmacokinetic and structure-activity relationship studies are presented. (C) 2011 Elsevier Ltd. All rights reserved.
• <i>Z</i>- and <i>E</i>-selective Horner–Wadsworth–Emmons reactions
  作者：Katalin Molnár、László Takács、Mihály Kádár、Ferenc Faigl、Zsuzsanna Kardos

  DOI：10.1080/00397911.2017.1319487

  日期：2017.7.3

  In the present work, we determined and evaluated the stereochemical outcome of the Horner-Wadsworth-Emmons (HWE) reaction of 2-oxoalkylphosphonates with different ester functions (bis(2,2,2-trifluoroethyl), 2,2,2-trifluoroethyl methyl, dimethyl) and side chains (aliphatic, aromatic) with three different aldehydes (benzaldehyde, THP- and PPB-protected Corey aldehydes) under two reaction conditions. The trans protocol is generally used in the E-selective HWE reactions, while cis protocol promotes the Z-selectivity.[GRAPHICS].