1-pyridin-4-yl-2-(triphenyl-λ⁵-phiosphanylidene)ethanone | 316124-45-5

• 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: 1-pyridin-4-yl-2-(triphenyl-λ⁵-phiosphanylidene)ethanone
• 英文别名: 1-pyridin-4-yl-2-(triphenyl-λ⁵-phosphanylidene)ethanone；(4-pyridyl)carbonylmethylidenetriphenylphosphorane；1-Pyridin-4-yl-2-(triphenyl-lambda*5*-phosphanylidene)-ethanone；1-pyridin-4-yl-2-(triphenyl-λ5-phosphanylidene)ethanone
• CAS: 316124-45-5
• 化学式: C₂₅H₂₀NOP
• 分子量: 381.414
• InChiKey: AHGULURYXBDUBY-UHFFFAOYSA-N

物化性质

• 熔点：
  224 °C
• 沸点：
  568.3±42.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-pyridin-4-yl-2-(triphenyl-λ⁵-phiosphanylidene)ethanone 在 4 A molecular sieve 作用下， 以 二氯甲烷 、 溶剂黄146 、 甲苯 为溶剂， 反应 2.75h， 生成 [3-(pyridin-4-ylcarbonyl)bicyclo[3.2.1]hept-5-en-2-yl]pyridin-4-ylmethanone
  参考文献：
  名称：

  1,3-Diaryl-4,5,6,7-tetrahydro-2H-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite

  摘要：

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.

  DOI：

  10.1021/jm990965x
• 作为产物：
  描述：

  4-(溴乙酰基)吡啶氢溴酸盐 在 三乙胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 1-pyridin-4-yl-2-(triphenyl-λ⁵-phiosphanylidene)ethanone
  参考文献：
  名称：

  Synthesis of Glycolysis Inhibitor PFK15 and Its Synergistic Action with an Approved Multikinase Antiangiogenic Drug on Human Endothelial Cell Migration and Proliferation

  摘要：

  活化的内皮细胞、免疫细胞和癌细胞更喜欢通过糖酵解来获取能量，以用于增殖和迁移。因此，阻断糖酵解是一种很有前景的抗癌和抗自身免疫性疾病进展的策略。糖酵解酶 PFKFB3（6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶）失活会抑制糖酵解水平，导致癌细胞（肿瘤发生）和内皮细胞（血管生成）的增殖和迁移减少。最近开发出了几种糖酵解抑制剂，其中(E)-1-(吡啶-4-基)-3-(喹啉-2-基)丙-2-烯-1-酮（PFK15）被认为是最有前途的抑制剂之一。众所周知，PFK15 可减少内皮细胞对葡萄糖的吸收，并有效阻止病理性血管生成。然而，目前还没有研究充分描述了 PFK15 的合成过程，从而使其能够普遍使用。本文提供了制备 PFK15 及其高级表征的所有必要细节。另一方面，已知的酪氨酸激酶抑制剂（如舒尼替尼）可影响其他分子靶点并有效阻断血管生成。我们从生物学角度研究并证实了同时服用糖酵解抑制剂 PFK15 和多激酶抑制剂舒尼替尼对 HUVEC 增殖和迁移的协同抑制作用。我们的研究结果表明，抑制内皮细胞的糖酵解活性与阻断生长因子受体相结合是一种很有前景的抗血管生成治疗方法。

  DOI：

  10.3390/ijms232214295

文献信息

• Enantio- and Diastereoselective Organocatalytic Conjugate Additions of Nitroalkanes to Enone Diesters
  作者：Matthew A. Horwitz、Jennifer L. Fulton、Jeffrey S. Johnson

  DOI：10.1021/acs.orglett.7b02735

  日期：2017.11.3

  catalyzed the addition reaction with consistently excellent stereoselectivities and yields across a wide range of substrates. By the use of the gem-diester functional handle present in the adducts, local desymmetrization via diastereotopic group discrimination was demonstrated, and a polyfunctionalized lactam with three contiguous stereocenters was synthesized.

  报道了硝基乙烷或硝基丙烷与烯酮二酯之间的对映体和非对映体选择性共轭加成反应。双功能三芳基次膦酸酯催化加成反应，具有稳定的立体选择性，并能在广泛的底物上产生收率。通过使用加合物中存在的宝石-二酯功能手柄，证明了通过非对映异构基团区分进行局部去对称化，并合成了具有三个连续立体中心的多官能内酰胺。
• [EN] PFKFB3 INHIBITOR AND METHODS OF USE AS AN ANTI-CANCER THERAPEUTIC<br/>[FR] INHIBITEUR DE PFKFB3 ET PROCÉDÉS D'UTILISATION EN TANT QUE PRODUIT THÉRAPEUTIQUE ANTICANCÉREUX
  申请人：ADVANCED CANCER THERAPEUTICS LLC

  公开号：WO2013148228A1

  公开（公告）日：2013-10-03

  A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one, is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells.

  本文提供了一种新的化合物，即(E)-1-(吡啶-4-基)-3-(7-(三氟甲基)喹啉-2-基)-丙-2-烯-1-酮。 (E)-1-(吡啶-4-基)-3-(7-(三氟甲基)喹啉-2-基)-丙-2-烯-1-酮是6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶3 (PFKFB3)的抑制剂，在体外和体内具有惊人的优越疗效和药效学特性。还提供了包括该化合物的制药组合物以及在体内治疗癌症和肿瘤，以及抑制细胞中糖酵解通量和PFKFB3酶活性的方法。
• New aspects of the aldol condensation of acetylpyridines with aromatic aldehydes
  作者：S. Z. Vatsadze、V. N. Nuriev、I. F. Leshcheva、N. V. Zyk

  DOI：10.1023/b:rucb.0000037863.85554.35

  日期：2004.4

  Aldol condensation of acetylpyridines with aromatic aldehydes was studied. A series of new products of cascade reactions were isolated and characterized.

  研究了乙酰吡啶与芳香醛的羟醛缩合。分离并表征了一系列级联反应的新产物。
• PFKFB3 inhibitor and methods of use as an anti-cancer therapeutic
  申请人：ADVANCED CANCER THERAPEUTICS, LLC

  公开号：US09649305B2

  公开（公告）日：2017-05-16

  A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one, is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells.

  本文提供了一种新的化合物，即(E)-1-(吡啶-4-基)-3-(7-(三氟甲基)喹啉-2-基)-丙-2-烯-1-酮。该化合物是6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3 (PFKFB3)的抑制剂，在体内外具有惊人的优越疗效和药效学特性。此外，还提供了包括该化合物的制药组合物以及在体内治疗癌症和肿瘤，以及在细胞中抑制糖酵解通量和PFKFB3酶活性的使用方法。
• PFKFB3 INHIBITOR AND METHODS OF USE AS AN ANTI-CANCER THERAPEUTIC
  申请人：ADVANCED CANCER THERAPEUTICS, LLC

  公开号：US20150064175A1

  公开（公告）日：2015-03-05

  A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one, is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells.

  本文提供了一种新化合物，即(E)-1-(吡啶-4-基)-3-(7-(三氟甲基)喹啉-2-基)-丙-2-烯-1-酮。 (E)-1-(吡啶-4-基)-3-(7-(三氟甲基)喹啉-2-基)-丙-2-烯-1-酮是6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3 (PFKFB3)的抑制剂，在体外和体内具有惊人的优越疗效和药理学特性。还提供了包括该化合物的制药组合物以及使用该化合物在体内治疗癌症和肿瘤以及抑制细胞中的糖酵解通量和PFKFB3酶活性的方法。