sodium 4-(acetamidomethyl)benzenesulfinate | 857003-04-4

• 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: sodium 4-(acetamidomethyl)benzenesulfinate
• 英文别名: Sodium 4-(acetamidomethyl)benzenesulfinate；sodium;4-(acetamidomethyl)benzenesulfinate
• CAS: 857003-04-4
• 化学式: C₉H₁₀NO₃S*Na
• 分子量: 235.239
• InChiKey: JEMVISCGFIMHKY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.44
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  sodium 4-(acetamidomethyl)benzenesulfinate 在 盐酸 、 copper diacetate 、 potassium carbonate 作用下， 以 二甲基亚砜 、 异丙醇 为溶剂， 反应 32.0h， 生成 (4-(苯基磺酰基)苯基)甲胺
  参考文献：
  名称：

  发现有效和有效的含氰基胍的烟酰胺磷酸核糖基转移酶（Nampt）抑制剂

  摘要：

  利用含酰胺化合物（4）与烟酰胺磷酸核糖基转移酶（Nampt）蛋白的共晶体结构和分子建模，设计并发现了一种有效的新型含砜基氰基抑制剂，该抑制剂带有砜部分（5，Nampt Biochemical IC 50  ＝ 2.5nM，A2780细胞增殖IC 50  ＝ 9.7nM。SAR的进一步探索发现了另外几种具有高效能和良好微粒体稳定性的含氰基胍的化合物。其中，化合物15选择用于体内谱分析并在小鼠中证明良好的口服暴露。当在A2780卵巢肿瘤异种移植模型中口服给药时，它还表现出优异的体内抗肿瘤功效。还确定了该化合物与NAMPT蛋白复合的共晶体结构。

  DOI：

  10.1016/j.bmcl.2013.11.006
• 作为产物：
  描述：

  4-(乙酰氨基甲基)苯磺酰氯 在 碳酸氢钠 、 sodium sulfite 作用下， 以 水 为溶剂， 反应 2.0h， 生成 sodium 4-(acetamidomethyl)benzenesulfinate
  参考文献：
  名称：

  [EN] GUANIDINE COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
  [FR] COMPOSÉS ET COMPOSITIONS DE GUANIDINE POUR L'INHIBITION DE NAMPT

  摘要：

  本发明涉及用于抑制NAMPT的化合物和组合物、它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示。

  公开号：

  WO2012031199A1

文献信息

• [EN] NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS POUR L'INHIBITION DE NAMPT
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2012031197A1

  公开（公告）日：2012-03-08

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，以及它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示：
• NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
  申请人：Bair Kenneth W.

  公开号：US20130295051A1

  公开（公告）日：2013-11-07

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below.

  本发明涉及用于抑制NAMPT的化合物和组合物、它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示。
• Compounds and compositions for the inhibition of NAMPT
  申请人：Forma TM, LLC

  公开号：US10272072B2

  公开（公告）日：2019-04-30

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及抑制 NAMPT 的化合物和组合物、其合成、应用和解毒剂。本发明的一种说明性化合物如下所示：
• Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
  作者：Peter S. Dragovich、Kenneth W. Bair、Timm Baumeister、Yen-Ching Ho、Bianca M. Liederer、Xiongcai Liu、Yongbo Liu、Thomas O’Brien、Jason Oeh、Deepak Sampath、Nicholas Skelton、Leslie Wang、Weiru Wang、Hongxing Wu、Yang Xiao、Po-wai Yuen、Mark Zak、Lei Zhang、Xiaozhang Zheng

  DOI：10.1016/j.bmcl.2013.06.090

  日期：2013.9

  Potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors containing 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas were identified using structure-based design techniques. The new compounds displayed improved aqueous solubilities, determined using a high-throughput solubility assessment, relative to previously disclosed urea and amide-containing NAMPT inhibitors. An optimized 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived compound exhibited potent anti-NAMPT activity (18; BC NAMPT IC50 = 11 nM; PC-3 antiproliferative IC50 = 36 nM), satisfactory mouse PK properties, and was efficacious in a PC-3 mouse xenograft model. The crystal structure of another optimized compound (29; NAMPT IC50 = 10 nM; A2780 antiproliferative IC50 = 7 nM) in complex with the NAMPT protein was also determined. (C) 2013 Elsevier Ltd. All rights reserved.
• Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
  作者：Xiaozhang Zheng、Kenneth W. Bair、Paul Bauer、Timm Baumeister、Krista K. Bowman、Alexandre J. Buckmelter、Maureen Caligiuri、Karl H. Clodfelter、Yezhen Feng、Bingsong Han、Yen-Ching Ho、Nikolai Kley、Hong Li、Xiaorong Liang、Bianca M. Liederer、Jian Lin、Justin Ly、Thomas O’Brien、Jason Oeh、Angela Oh、Dominic J. Reynolds、Deepak Sampath、Geeta Sharma、Nicholas Skelton、Chase C. Smith、Jarrod Tremayne、Leslie Wang、Weiru Wang、Zhongguo Wang、Hongxing Wu、Jiansheng Wu、Yang Xiao、Guangxing Yang、Po-wai Yuen、Mark Zak、Peter S. Dragovich

  DOI：10.1016/j.bmcl.2013.08.074

  日期：2013.10

  Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained. (C) 2013 Elsevier Ltd. All rights reserved.