2-甲基-2-丙基2-乙酰基肼羧酸酯 | 90271-04-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-甲基-2-丙基2-乙酰基肼羧酸酯
• 英文名称: N'-acetylhydrazinecarboxylic acid tert-butyl ester
• 英文别名: N-acetyl-N′-Boc-hydrazine；tert.-Butyl-2-acetyl-carbazat；tert-butyl N-acetamidocarbamate
• CAS: 90271-04-8
• 化学式: C₇H₁₄N₂O₃
• mdl: MFCD18206107
• 分子量: 174.2
• InChiKey: PWKMRSZXDDOMEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基2-乙酰基肼羧酸酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以1.0 g的产率得到乙酰肼
  参考文献：
  名称：

  Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal

  摘要：

  A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00146-x
• 作为产物：
  描述：

  肼基甲酸叔丁酯 、 乙酸酐 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以0.95 g的产率得到2-甲基-2-丙基2-乙酰基肼羧酸酯
  参考文献：
  名称：

  Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal

  摘要：

  A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00146-x

文献信息

• Design and Discovery of 6-[(3<i>S</i>,4<i>S</i>)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2<i>H</i>-pyran-4-yl)-1,5-dihydro-4<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidin-4-one (PF-04447943), a Selective Brain Penetrant PDE9A Inhibitor for the Treatment of Cognitive Disorders
  作者：Patrick R. Verhoest、Kari R. Fonseca、Xinjun Hou、Caroline Proulx-LaFrance、Michael Corman、Christopher J. Helal、Michelle M. Claffey、Jamison B. Tuttle、Karen J. Coffman、Shenpinq Liu、Frederick Nelson、Robin J. Kleiman、Frank S. Menniti、Christopher J. Schmidt、Michelle Vanase-Frawley、Spiros Liras

  DOI：10.1021/jm3007799

  日期：2012.11.8

  hyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic

  6-[（3 S，4 S）-4-甲基-1-（嘧啶-2-基甲基）吡咯烷-3-基] -1-（四氢-2 H-吡喃-4-基）-1,5-二氢-4 H-吡唑并[3,4- d] pyrimidin-4-one（PF-04447943）是使用平行合成化学和基于结构的药物设计（SBDD）鉴定的新型PDE9A抑制剂，已进入临床试验。通过针对PDE9A和PDE1C催化位点之间的关键残基差异，可以实现PDE9A对其他PDE家族成员的选择性。优化了该系列的理化特性，以在包括人类在内的多个物种中提供出色的体外和体内药代动力学特性。据报道会提高啮齿动物的大脑和脑脊液中的中央cGMP水平。此外，它在几种啮齿动物模型中表现出认知活性，在淀粉样前体蛋白（APP）转基因小鼠模型中表现出突触稳定作用。
• AMINO-HETEROCYCLIC COMPOUNDS
  申请人：Verhoest Patrick R.

  公开号：US20090030003A1

  公开（公告）日：2009-01-29

  The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R, R 1 , R 2 and R 3 are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.

  该发明提供了式（I）的PDE9抑制化合物及其药用盐，其中R、R1、R2和R3如本文所定义。还提供了含有式I化合物的药物组合物，并将其用于治疗神经退行性和认知障碍，如阿尔茨海默病和精神分裂症。
• Topographically constrained aromatic α-aza-amino acids. Synthesis, molecular structure, and conformation of two azaTic derivatives
  作者：Ines Torrini、Giampiero Pagani Zecchini、Mario Paglialunga Paradisi、Gino Lucente、Gaia Mastropietro、Enrico Gavuzzo、Fernando Mazza、Giorgio Pochetti

  DOI：10.1016/s0040-4020(97)10267-8

  日期：1998.1

  oxylic acid (azaTic) is a new conformationally restricted analogue of phenylalanine which, due to its α-aza-nature, should allow, in addition to the topographical control typical of the Tic residue, a definite local perturbation of the backbone conformation. Two azaTic models, namely azaTic-NH2 (2) and MeCO-azaTic-NHMe (5), have been synthesized and their conformation has been determined and compared

  3,4-二氢-2（1 H）-邻苯二甲酰基羧酸（azaTic）是苯丙氨酸的一种新的构象受限类似物，由于其α-氮杂性质，除Tic残基的典型形貌控制外，它还应允许，主干构象的确定局部扰动。已经合成了两个azaTic模型，即azaTic-NH 2（2）和MeCO-azaTic-NHMe（5），并确定了其构象并将其与相关Tic和azaPro模型的构象进行比较。
• Mitotic Kinesin Inhibitors and Methods of Use Thereof
  申请人：Hans Jeremy

  公开号：US20080182992A1

  公开（公告）日：2008-07-31

  This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

  本发明涉及有丝分裂动力蛋白酶抑制剂，特别是KSP的抑制剂，以及制备这些抑制剂的方法。该发明还提供了包含该发明抑制剂的药物组合物，并且提供了利用该发明抑制剂和药物组合物在治疗和预防各种疾病中的方法。
• Compounds with growth hormone releasing properties
  申请人：Novo Nordisk A/S

  公开号：US06083908A1

  公开（公告）日：2000-07-04

  Compounds of Formula I ##STR1## and their use for treating medical disorders resulting from a deficiency in growth hormone are disclosed, wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.4a, R.sup.5a, G, J and D are as defined in the specification.

  公开了式I的化合物及其用于治疗由生长激素缺乏引起的医学疾病，其中R.sup.1、R.sup.2、R.sup.3a、R.sup.4a、R.sup.5a、G、J和D如规范中所定义。