N,N'-bis(tert-butoxycarbonyl)-N-(pyridin-4-yl)hydrazine | 614717-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N,N'-bis(tert-butoxycarbonyl)-N-(pyridin-4-yl)hydrazine
• 英文别名: tert-butyl N-[(2-methylpropan-2-yl)oxycarbonylamino]-N-pyridin-4-ylcarbamate
• CAS: 614717-75-8
• 化学式: C₁₅H₂₃N₃O₄
• 分子量: 309.365
• InChiKey: UHKACACYYHDZJW-UHFFFAOYSA-N

物化性质

• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N'-bis(tert-butoxycarbonyl)-N-(pyridin-4-yl)hydrazine 在 盐酸 作用下， 以 1,4-二氧六环 、 异丙醇 为溶剂， 生成 4-肼基吡啶盐酸盐
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r
• 作为产物：
  描述：

  4-溴吡啶 、 偶氮二甲酸二叔丁酯 在 仲丁基锂 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 生成 N,N'-bis(tert-butoxycarbonyl)-N-(pyridin-4-yl)hydrazine
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r

文献信息

• Synthesis of 17-α-Substituted Estradiol-Pyridin-2-yl Hydrazine Conjugates as Effective Ligands for Labeling with Alberto's Complex <i>f</i><i>ac</i>-[Re(OH₂)₃(CO)₃]⁺ in Water
  作者：Jeffrey B. Arterburn、Cesear Corona、Kalla Venkateswara Rao、Kathryn E. Carlson、John A. Katzenellenbogen

  DOI：10.1021/jo034780g

  日期：2003.9.1

  hydrochloride salt 25. The 17alpha-estradiol-tricarbonylrhenium(I) complex 4 was synthesized by labeling 25 with fac-[Re(OH(2))(3)(CO)(3)](+) in aqueous ethanol. This complex exhibited excellent stability and high receptor binding affinity for the estrogen receptor, and it is a promising model for evaluation of the analogous Tc-99m complexes as diagnostic imaging agents for breast tumors.

  （99m）Tc-雌二醇放射性药物的开发将有利于检测雌激素受体阳性的乳腺肿瘤。与有机金属三羰基-Tc（I）和相关的Re（I）配合物共轭的雌二醇衍生物能够实现高受体结合亲和力，但是在水中合成放射性标记配合物的有效方法尚不可用。我们对2-肼基吡啶作为Tc和Re的配体的合成的兴趣使我们研究了Pd催化卤代吡啶底物与肼基二甲酸二叔丁酯的胺化反应。2-和4-取代的卤代吡啶底物均经过与偶氮二甲酸二叔丁酯的CN偶联反应，生成Boc保护的吡啶肼衍生物。仅高度亲电子的3-吡啶卤化物被转化为肼。Boc保护的5-溴吡啶-2-基肼底物3是通过在2，5-二溴吡啶的2-位进行区域选择性取代而制备的。使用Sonogashira和Suzuki / Miyaura偶联反应分别以高收率合成1和2，将这种双功能螯合物连接到雌二醇的17alpha位置的乙炔基或乙烯基上。在酸性条件下将1脱保护得到肼盐酸盐25。通过用fac- [Re（
• Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate
  作者：John Regan、Steffen Breitfelder、Pier Cirillo、Thomas Gilmore、Anne G. Graham、Eugene Hickey、Bernhard Klaus、Jeffrey Madwed、Monica Moriak、Neil Moss、Chris Pargellis、Sue Pav、Alfred Proto、Alan Swinamer、Liang Tong、Carol Torcellini

  DOI：10.1021/jm020057r

  日期：2002.7.1

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.