lithium 1-propyl-1H-pyrazole-4-sulfinate | 1450723-63-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: lithium 1-propyl-1H-pyrazole-4-sulfinate
• 英文别名: Lithium;1-propylpyrazole-4-sulfinate；lithium;1-propylpyrazole-4-sulfinate
• CAS: 1450723-63-3
• 化学式: C₆H₉N₂O₂S*Li
• 分子量: 180.157
• InChiKey: GAHIBZFCZYGHAG-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.46
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  lithium 1-propyl-1H-pyrazole-4-sulfinate 在 ammonium hydroxide 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 furo[2,3-c]pyridin-2-carboxylic acid [5-(1-propyl-1H-pyrazol-4-sulfonyl)pyridin-2-ylmethyl]amide
  参考文献：
  名称：

  Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility

  摘要：

  Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD(7.4) was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.026
• 作为产物：
  描述：

  4-溴-1-丙基-1H-吡唑 在 正丁基锂 、 二氧化硫 作用下， 以 乙醚 为溶剂， 反应 1.75h， 以27%的产率得到lithium 1-propyl-1H-pyrazole-4-sulfinate
  参考文献：
  名称：

  [EN] CYCLOPROPYL AMIDE DERIVATIVES
  [FR] DÉRIVÉS D'AMIDE CYCLOPROPYLE

  摘要：

  本发明涉及某些环丙基酰胺化合物，包括这些化合物的药物组合物，以及使用这些化合物和药物组合物治疗白血病和实体肿瘤、炎症性疾病、骨质疏松症、动脉粥样硬化、肠易激综合征和其他疾病和医疗状况的方法。本发明还涉及某些环丙基酰胺化合物用于抑制烟酰胺磷酸核糖转移酶（"NAMPT"）。

  公开号：

  WO2014074715A1

文献信息

• [EN] CYCLOPROPYL AMIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMIDE CYCLOPROPYLE
  申请人：GENENTECH INC

  公开号：WO2014074715A1

  公开（公告）日：2014-05-15

  The present invention relates to certain cyclopropyl amide compounds, pharmaceutical compositions comprising such compounds, and methods of treating cancer, including leukemias and solid tumors, inflammatory diseases, osteoporosis, atherosclerosis, irritable bowel syndrome, and other diseases and medical conditions, with such compounds and pharmaceutical compositions. The present invention also relates to certain cyclopropyl amide compounds for use in inhibiting nicotinamide phosphoribosyltransferase ("NAMPT").

  本发明涉及某些环丙基酰胺化合物，包括这些化合物的药物组合物，以及使用这些化合物和药物组合物治疗白血病和实体肿瘤、炎症性疾病、骨质疏松症、动脉粥样硬化、肠易激综合征和其他疾病和医疗状况的方法。本发明还涉及某些环丙基酰胺化合物用于抑制烟酰胺磷酸核糖转移酶（"NAMPT"）。
• Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility
  作者：Mark Zak、Bianca M. Liederer、Deepak Sampath、Po-wai Yuen、Kenneth W. Bair、Timm Baumeister、Alexandre J. Buckmelter、Karl H. Clodfelter、Eric Cheng、Lisa Crocker、Bang Fu、Bingsong Han、Guangkun Li、Yen-Ching Ho、Jian Lin、Xiongcai Liu、Justin Ly、Thomas O’Brien、Dominic J. Reynolds、Nicholas Skelton、Chase C. Smith、Suzanne Tay、Weiru Wang、Zhongguo Wang、Yang Xiao、Lei Zhang、Guiling Zhao、Xiaozhang Zheng、Peter S. Dragovich

  DOI：10.1016/j.bmcl.2014.12.026

  日期：2015.2

  Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD(7.4) was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies. (C) 2014 Elsevier Ltd. All rights reserved.