(4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)methanamine | 1374864-79-5

• 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: (4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)methanamine
• 英文别名: [4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methanamine
• CAS: 1374864-79-5
• 化学式: C₁₄H₁₂F₃NO₂S
• 分子量: 315.316
• InChiKey: SCTQRRLDEZKHRH-UHFFFAOYSA-N

物化性质

• 沸点：
  438.9±45.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)methanamine 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 生成 N-[[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.06.090
• 作为产物：
  描述：

  3-(三氟甲基)苯硼酸 在 盐酸 、 copper diacetate 、 potassium carbonate 、 二甲基亚砜 作用下， 以 异丙醇 为溶剂， 反应 32.0h， 生成 (4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)methanamine
  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

文献信息

• [EN] BISARYLSULFONE AND DIALKYLARYLSULFONE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS<br/>[FR] COMPOSÉS DE BISARYLSULFONE ET DE DIALKYLARYLSULFONE EN TANT QUE BLOQUANTS DU CANAL CALCIQUE
  申请人：ZALICUS PHARMACEUTICALS LTD

  公开号：WO2012061926A1

  公开（公告）日：2012-05-18

  The invention relates to bisarylsulfone and dialkylarylsulfone compounds (e.g., compounds according to any of Formulas (I)-(IX) or compounds (1)-(227) of Tables 4 and 5) useful in treating conditions associated with calcium channel function, and particularly conditions associated with N-type calcium channel activity. The invention also relates to pharmaceutical compositions that include these bisarylsulfone compounds, as well methods for the treatment of conditions such as cardiovascular disease, epilepsy, cancer and pain.

  这项发明涉及对双芳基砜和二烷基芳基砜化合物（例如，符合任何公式（I）-（IX）或表4和5中化合物（1）-（227）的化合物）的用途，用于治疗与钙通道功能有关的疾病，特别是与N型钙通道活性有关的疾病。该发明还涉及包括这些双芳基砜化合物的药物组合物，以及用于治疗心血管疾病、癫痫、癌症和疼痛等疾病的方法。
• BISARYLSULFONE AND DIALKYLARYLSULFONE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS
  申请人：Pajouhesh Hassan A.

  公开号：US20140113898A1

  公开（公告）日：2014-04-24

  The invention relates to bisarylsulfone and dialkylarylsulfone compounds (e.g., compounds according to any of Formulas (I)-(IX) or compounds (1)-(227) of Tables 4 and 5) useful in treating conditions associated with calcium channel function, and particularly conditions associated with N-type calcium channel activity. The invention also relates to pharmaceutical compositions that include these bisarylsulfone compounds, as well methods for the treatment of conditions such as cardiovascular disease, epilepsy, cancer and pain.

  本发明涉及双芳基砜和二烷基芳基砜化合物（例如，根据任何公式（I）-（IX）或表4和5的化合物（1）-（227）的化合物），其可用于治疗与钙通道功能有关的疾病，特别是与N型钙通道活性有关的疾病。本发明还涉及包括这些双芳基砜化合物的制药组合物，以及用于治疗心血管疾病、癫痫、癌症和疼痛等疾病的方法。
• 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.
• Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors
  作者：Xiaozhang Zheng、Paul Bauer、Timm Baumeister、Alexandre J. Buckmelter、Maureen Caligiuri、Karl H. Clodfelter、Bingsong Han、Yen-Ching Ho、Nikolai Kley、Jian Lin、Dominic J. Reynolds、Geeta Sharma、Chase C. Smith、Zhongguo Wang、Peter S. Dragovich、Janet Gunzner-Toste、Bianca M. Liederer、Justin Ly、Thomas O’Brien、Angela Oh、Leslie Wang、Weiru Wang、Yang Xiao、Mark Zak、Guiling Zhao、Po-wai Yuen、Kenneth W. Bair

  DOI：10.1021/jm4008664

  日期：2013.8.22

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.
• 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.