1-aminocyclobutanecarboxamide

• 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
• 英文名称: 1-aminocyclobutanecarboxamide
• 英文别名: 1-aminocyclobutane-1-carboxamide
• 化学式: C₅H₁₀N₂O
• mdl: MFCD12817056
• 分子量: 114.147
• InChiKey: SILFUQGFSMYYME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-aminocyclobutanecarboxamide 在 盐酸 作用下， 反应 20.0h， 以90%的产率得到1-氨基-1-环丁基羧酸盐酸盐
  参考文献：
  名称：

  First synthesis of (1S,2S)- and (1R,2R)-1-amino-2-isopropylcyclobutanecarboxylic acids by asymmetric Strecker reaction from 2-substituted cyclobutanones

  摘要：

  An efficient and easy one-pot reaction from readily available racemic 2-substituted cyclobutanones gave, by means of asymmetric Strecker synthesis in the presence of an amine chiral auxiliary, two major aminonitriles with excellent diastereoselectivity. After separation, the major cis-aminonitriles were hydrolysed and hydrogenolysed to lead for the first time to pure non-racemic (+)-1-amino-2-isopropylcyclobutanecarboxylic acid (ACBC) and its antipode. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00073-9
• 作为产物：
  描述：

  (1'S)-1-[(1'-methylbenzyl)amino]cyclobutanecarbonitrile 在 palladium dihydroxide 硫酸 、 氢气 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 1-aminocyclobutanecarboxamide
  参考文献：
  名称：

  First synthesis of (1S,2S)- and (1R,2R)-1-amino-2-isopropylcyclobutanecarboxylic acids by asymmetric Strecker reaction from 2-substituted cyclobutanones

  摘要：

  An efficient and easy one-pot reaction from readily available racemic 2-substituted cyclobutanones gave, by means of asymmetric Strecker synthesis in the presence of an amine chiral auxiliary, two major aminonitriles with excellent diastereoselectivity. After separation, the major cis-aminonitriles were hydrolysed and hydrogenolysed to lead for the first time to pure non-racemic (+)-1-amino-2-isopropylcyclobutanecarboxylic acid (ACBC) and its antipode. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00073-9

文献信息

• Probing Mercaptobenzamides as HIV Inactivators via Nucleocapsid Protein 7
  作者：Mrinmoy Saha、Michael T. Scerba、Nathaniel I. Shank、Tracy L. Hartman、Caitlin A. Buchholz、Robert W. Buckheit、Stewart R. Durell、Daniel H. Appella

  DOI：10.1002/cmdc.201700141

  日期：2017.5.22

  significant challenge. In this study, a series of novel 2-mercaptobenzamide prodrugs were investigated for anti-HIV activity in the context of NCp7 inactivation. The molecules were synthesized from the corresponding thiosalicylic acids, and they are all crystalline solids and stable at room temperature. Derivatives with a range of amide side chains and aromatic substituents were synthesized and screened

  人免疫缺陷病毒1型（HIV-1）核衣壳蛋白7（NCp7）是锌指蛋白，在病毒复制和成熟中起关键作用，并且是药物开发的有吸引力的靶标。但是，抑制NCp7的药物样分子的开发一直是一项重大挑战。在这项研究中，研究了一系列新型的2-巯基苯甲酰胺前药在NCp7失活的情况下的抗HIV活性。这些分子是由相应的硫代水杨酸合成的，它们都是结晶固体，在室温下稳定。合成了具有一系列酰胺侧链和芳族取代基的衍生物，并筛选了抗HIV活性。观察到广泛的抗病毒活性，根据芳香环和侧链上取代基的细微变化，IC5​​0值范围为1至100μm。这些结构-活性关系的结果适合细胞内激活和与NCp7相互作用的可能模式，以解释抗病毒活性的变化。我们生产一系列巯基苯甲酰胺前药的策略代表了制备可筛选抗HIV活性文库的总体新方向。
• 一种制备阿帕鲁胺中间体及阿帕鲁胺的方法
  申请人：南京方生和医药科技有限公司

  公开号：CN113292535B

  公开（公告）日：2022-07-01

  本发明涉及一种制备阿帕鲁胺中间体及阿帕鲁胺的方法，以式(5)所示化合物作为中间体制备阿帕鲁胺，式(5)所示化合物的制备方法包括使式(3)所示化合物式(4)所示化合物以及硫代试剂发生反应生成式(5)所示化合物的步骤；所述硫代试剂为硫代氯甲酸苯酯、N,N’‑硫代羰基二咪唑、1,1‑硫代羰基DI‑2(1H)‑吡啶中的一种或多种的组合。发明人通过大量实验研究意外发现，适当的条件下，4‑(1‑羧酰胺‑环丁氨基)‑2‑氟‑N‑甲基‑苯甲酰胺、5‑氨基‑2‑氰基‑3‑三氟甲基吡啶、硫代氯甲酸苯酯三者通过一步反应就可以比现有技术明显更高的收率获得阿帕鲁胺，且保持甚至提高了阿帕鲁胺的纯度。基于此发现，经过进一步研究，得到和提出本发明。
• Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: Improving selectivity over hERG
  作者：Zoran Rankovic、Jiaqiang Cai、Jennifer Kerr、Xavier Fradera、John Robinson、Ashvin Mistry、William Finlay、George McGarry、Fiona Andrews、Wilson Caulfield、Iain Cumming、Maureen Dempster、John Waller、Wullie Arbuckle、Mark Anderson、Iain Martin、Ann Mitchell、Clive Long、Mark Baugh、Paul Westwood、Emma Kinghorn、Phil Jones、Joost C.M. Uitdehaag、Mario van Zeeland、Dominique Potin、Laurent Saniere、Andre Fouquet、François Chevallier、Hortense Deronzier、Cecile Dorleans、Eric Nicolai

  DOI：10.1016/j.bmcl.2010.08.101

  日期：2010.11

  Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of c log P and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1<i>H</i>-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an Active Metabolite. A Novel, Potent and Selective Cannabinoid-1 Receptor Inverse Agonist with High Antiobesity Efficacy in DIO Mice
  作者：Chien-Huang Wu、Ming-Shiu Hung、Jen-Shin Song、Teng-Kuang Yeh、Ming-Chen Chou、Cheng-Ming Chu、Jiing-Jyh Jan、Min-Tsang Hsieh、Shi-Liang Tseng、Chun-Ping Chang、Wan-Ping Hsieh、Yinchiu Lin、Yen-Nan Yeh、Wan-Ling Chung、Chun-Wei Kuo、Chin-Yu Lin、Horng-Shing Shy、Yu-Sheng Chao、Kak-Shan Shia

  DOI：10.1021/jm900471u

  日期：2009.7.23

  By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB I inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.
• First synthesis of (1S,2S)- and (1R,2R)-1-amino-2-isopropylcyclobutanecarboxylic acids by asymmetric Strecker reaction from 2-substituted cyclobutanones
  作者：Molika Truong、Frédéric Lecornué、Antoine Fadel

  DOI：10.1016/s0957-4166(03)00073-9

  日期：2003.4

  An efficient and easy one-pot reaction from readily available racemic 2-substituted cyclobutanones gave, by means of asymmetric Strecker synthesis in the presence of an amine chiral auxiliary, two major aminonitriles with excellent diastereoselectivity. After separation, the major cis-aminonitriles were hydrolysed and hydrogenolysed to lead for the first time to pure non-racemic (+)-1-amino-2-isopropylcyclobutanecarboxylic acid (ACBC) and its antipode. (C) 2003 Elsevier Science Ltd. All rights reserved.