1-(β-hydroxyethyl)-5-(α-R-tert-butyloxycarbonylamino-β-benzyloxyethyl)tetrazole | 851118-47-3

• 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-(β-hydroxyethyl)-5-(α-R-tert-butyloxycarbonylamino-β-benzyloxyethyl)tetrazole
• 英文别名: tert-butyl N-[(1S)-1-[1-(2-hydroxyethyl)tetrazol-5-yl]-2-phenylmethoxyethyl]carbamate
• CAS: 851118-47-3
• 化学式: C₁₇H₂₅N₅O₄
• 分子量: 363.417
• InChiKey: CTZITPFPPWEKMX-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-Isocyanatobutyl benzoate 、 1-(β-hydroxyethyl)-5-(α-R-tert-butyloxycarbonylamino-β-benzyloxyethyl)tetrazole 在 D(+)-10-樟脑磺酸 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以87.5%的产率得到4-[2-[5-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylmethoxyethyl]tetrazol-1-yl]ethoxycarbonylamino]butyl benzoate
  参考文献：
  名称：

  Process for the preparation of tetrazol-derived compounds as growth hormone secretagogues

  摘要：

  描述了一种制备四唑衍生化合物的方法，这些化合物可用作生长激素分泌素。

  公开号：

  US20050096466A1
• 作为产物：
  描述：

  2-[5-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylmethoxyethyl]tetrazol-1-yl]ethyl acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 1-(β-hydroxyethyl)-5-(α-R-tert-butyloxycarbonylamino-β-benzyloxyethyl)tetrazole
  参考文献：
  名称：

  Design and synthesis of tetrazole-based growth hormone secretagogue: The SAR studies of the O-benzyl serine side chain

  摘要：

  The structure-activity relationship of the O-benzyl serine side chain was investigated based on the tetrazole-based growth hormone secretagogue BMS-317180 (2). The ortho position of the benzyl moiety was found to be favorable for introduction of substituents. A series of ortho-substituted compounds were synthesized with improved in-vitro and in-vivo activity. Among them, the biphenyl compound 2p shows twofold improvement in potency compared to its parent compound BMS- 317180 (2). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.021

文献信息

• Process Research and Development for a Tetrazole-Based Growth Hormone Secretagogue (GHS) Pharmaceutical Development Candidate
  作者：Akin H. Davulcu、Douglas D. McLeod、Jun Li、Kishta Katipally、Adam Littke、Wendel Doubleday、Zhongmin Xu、Cary W. McConlogue、Chiajen J. Lai、Margaret Gleeson、Mark Schwinden、Rodney L. Parsons

  DOI：10.1021/jo9003508

  日期：2009.6.5

  BMS-317180 (1) is a potent, orally active agonist of the human growth hormone secretagogue (GHS) receptor. This manuscript details the process research and development efforts that enabled the synthesis of the phosphate salt of 1 on a multi-kilogram scale. Key considerations in the development of this process focused on safe execution and the requirement for telescoped synthetic transformations (i.e., without isolation of intermediate products) to contend with a lack of suitably crystalline products.
• Process for the preparation of tetrazol-derived compounds as growth hormone secretagogues
  申请人：Schwinden D. Mark

  公开号：US20050096466A1

  公开（公告）日：2005-05-05

  A process for the preparation of tetrazole-derived compounds useful as growth hormone secretagogues is described.

  描述了一种制备四唑衍生化合物的方法，这些化合物可用作生长激素分泌素。
• Design and synthesis of tetrazole-based growth hormone secretagogue: The SAR studies of the O-benzyl serine side chain
  作者：Jun Li、Stephanie Y. Chen、Shiwei Tao、Haixia Wang、James J. Li、Steve Swartz、Christa Musial、Andres A. Hernandez、Neil Flynn、Brian J. Murphy、Blake Beehler、Kenneth E. Dickinson、Leah Giupponi、Gary Grover、Ramakrishna Seethala、Paul Sleph、Dorothy Slusarchyk、Mujing Yan、William G. Humphreys、Hongjian Zhang、William R. Ewing、Jeffrey A. Robl、David Gordon、Joseph A. Tino

  DOI：10.1016/j.bmcl.2008.02.021

  日期：2008.3

  The structure-activity relationship of the O-benzyl serine side chain was investigated based on the tetrazole-based growth hormone secretagogue BMS-317180 (2). The ortho position of the benzyl moiety was found to be favorable for introduction of substituents. A series of ortho-substituted compounds were synthesized with improved in-vitro and in-vivo activity. Among them, the biphenyl compound 2p shows twofold improvement in potency compared to its parent compound BMS- 317180 (2). (C) 2008 Elsevier Ltd. All rights reserved.