(S)-1-氰基-3-甲基丁胺 | 105356-41-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (S)-1-氰基-3-甲基丁胺
• 英文名称: (L)-2-Amino-4-methylvaleronitril
• 英文别名: (S)-1-cyano-3-methyl-butylamine；(2S)-2-amino-4-methylpentanenitrile
• CAS: 105356-41-0
• 化学式: C₆H₁₂N₂
• 分子量: 112.175
• InChiKey: ROAHGHLLRAUFEQ-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-1-氰基-3-甲基丁胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(tert-butyl)-N-((S)-1-(((S)-1-cyano-3-methylbutyl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Optimization strategy of single-digit nanomolar cross-class inhibitors of mammalian and protozoa cysteine proteases

  摘要：

  Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-based probes for diagnostic and mechanistic purposes that are critical in health and disease. In this paper, we present the modulation of a CP panel of parasites and mammals (Trypanosoma cruzi cruzain, LmCPB, CatK, CatL and CatS), whose inhibition by nitrile peptidomimetics allowed the identification of specificity and selectivity for a given CP. The activity cliffs identified at the CP inhibition level are useful for retrieving trends through multiple structure-activity relationships. For two of the cruzain inhibitors (10g and 4e), both enthalpy and entropy are favourable to Gibbs binding energy, thus overcoming enthalpy-entropy compensation (EEC). Group contribution of individual molecular modification through changes in enthalpy and entropy results in a separate partition on the relative differences of Gibbs binding energy (Delta Delta G). Overall, this study highlights the role of CPs in polypharmacology and multi-target screening, which represents an imperative trend in the actual drug discovery effort.

  DOI：

  10.1016/j.bioorg.2020.104039
• 作为产物：
  描述：

  Boc-L-亮氨酰胺 在 甲酸 、 N,N-二异丙基乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (S)-1-氰基-3-甲基丁胺
  参考文献：
  名称：

  Optimization strategy of single-digit nanomolar cross-class inhibitors of mammalian and protozoa cysteine proteases

  摘要：

  Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-based probes for diagnostic and mechanistic purposes that are critical in health and disease. In this paper, we present the modulation of a CP panel of parasites and mammals (Trypanosoma cruzi cruzain, LmCPB, CatK, CatL and CatS), whose inhibition by nitrile peptidomimetics allowed the identification of specificity and selectivity for a given CP. The activity cliffs identified at the CP inhibition level are useful for retrieving trends through multiple structure-activity relationships. For two of the cruzain inhibitors (10g and 4e), both enthalpy and entropy are favourable to Gibbs binding energy, thus overcoming enthalpy-entropy compensation (EEC). Group contribution of individual molecular modification through changes in enthalpy and entropy results in a separate partition on the relative differences of Gibbs binding energy (Delta Delta G). Overall, this study highlights the role of CPs in polypharmacology and multi-target screening, which represents an imperative trend in the actual drug discovery effort.

  DOI：

  10.1016/j.bioorg.2020.104039

文献信息

• The Synthesis of α-Aminonitriles Starting from the Corresponding Amino Acids. I. Use of<i>o</i>-Nitrophenylsulfenyl as an N-Protecting Group
  作者：Katsuhiro Kawashiro、Hideyuki Yoshida、Shiro Morimoto

  DOI：10.1246/bcsj.50.2956

  日期：1977.11

  N-o-Nitrophenylsulfenylamino acid amides of glycine, alanine (DL and L), leucine (DL and L), methionine (DL), phenylalanine (DL and L), and proline (L) were dehydrated in POCl3-pyridine. The N-protected α-amino-nitriles obtained were treated with anhydrous HCl affording the corresponding α-aminonitrile hydrochlorides. The optical purity of the L-α-aminonitriles was well retained.

  甘氨酸、丙氨酸（DL 和 L）、亮氨酸（DL 和 L）、甲硫氨酸 (DL)、苯丙氨酸 (DL 和 L) 和脯氨酸 (L) 的非硝基苯硫基氨基酸酰胺在 POCl3-吡啶中脱水。得到的 N-保护的 α-氨基腈用无水 HCl 处理，得到相应的 α-氨基腈盐酸盐。L-α-氨基腈的光学纯度保持良好。
• Peptide ligation by chemoselective aminonitrile coupling in water
  作者：Pierre Canavelli、Saidul Islam、Matthew W. Powner

  DOI：10.1038/s41586-019-1371-4

  日期：2019.7

  N-to-C peptide ligation. Our model unites prebiotic aminonitrile synthesis and biological α-peptides, suggesting that short N-acyl peptide nitriles were plausible substrates during early evolution.Prebiotic peptide formation is achieved through chemoselective, high-yielding ligation of α-aminonitriles in water, showing selectivity for α-peptide coupling and tolerance of all proteinogenic amino acid residues

  酰胺键的形成是化学和生物学中最重要的反应之一 1-4，但目前还没有化学方法可以在水中实现 α-肽连接，从而耐受肽连接位点的所有 20 种蛋白质氨基酸。通用遗传密码确立了肽的生物学作用早于生命最后一个普遍的共同祖先，并且肽在生命起源中发挥了重要作用5-9。硫在柠檬酸循环、非核糖体肽合成和聚酮化合物生物合成中的重要作用指向在生命进化过程中，硫酯依赖性肽连接先于 RNA 依赖性蛋白质合成 5,9-13。然而，尚未证明氨酰基硫酯形成的稳健机制。在这里，我们报告了一种化学选择性，高产 α-氨基腈连接，仅利用益生元合理的分子——硫化氢、硫代乙酸盐 12,14 和铁氰化物 12,14-17 或氰基乙炔 8,14——在水中产生 α-肽。这种连接对 α-氨基腈偶联具有极高的选择性，并能耐受所有 20 个蛋白质氨基酸残基。两个基本特征使肽能够在水中连接：α-氨基腈的反应性和 pKaH 使它们与中性 pH 值的
• Indole nitriles
  申请人：——

  公开号：US20040077646A1

  公开（公告）日：2004-04-22

  Compounds of the formula (I) 1 wherein m, n, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as described herein, together with methods for making the compounds and using the compounds for treatment of diseases or conditions mediated by Cathepsin K.

  式(I)的化合物，其中m、n、R1、R2、R3、R4、R5和R6如本文所述，以及制备这些化合物的方法和利用这些化合物治疗由Cathepsin K介导的疾病或症状的方法。
• Dipeptide nitriles
  申请人：Novartis AG

  公开号：US06353017B1

  公开（公告）日：2002-03-05

  N-terminal substituted dipeptide nitriles as defined are useful as inhibitors of cysteine cathepsins, e.g. cathepsins B, K, L and S, and can be used for the treatment of cysteine cathepsin dependent diseases and conditions, including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, tumors (especially tumor invasion and tumor metastasis), coronary disease, atherosclerosis (including atherosclerotic plaque rupture and destabilization). Particular dipeptide nitriles are compounds of formula I, or physiologically-acceptable and -cleavable esters or a salts thereof wherein: the symbols are as defined. In particular it has been found that by appropriate choice of groups R, R2, R3, R4, R5, X1, Y and L, the relative selectivity of the compounds as inhibitors of the various cysteine cathepsin types, e.g. cathepsins B, K, L and S may be altered, e.g. to obtain inhibitors which selectively inhibit a particular cathepsin type or combination of cathepsin types.

  N-末端取代二肽腈可作为半胱氨酸蛋白酶抑制剂，例如半胱氨酸蛋白酶B、K、L和S，并可用于治疗依赖于半胱氨酸蛋白酶的疾病和症状，包括炎症、类风湿关节炎、骨关节炎、骨质疏松、肿瘤（尤其是肿瘤侵袭和转移）、冠心病、动脉粥样硬化（包括动脉粥样硬化斑块破裂和不稳定）。特定的二肽腈化合物为公式I的化合物，或其生理上可接受和可裂解的酯或盐，其中：符号如定义。特别是发现通过适当选择基团R、R2、R3、R4、R5、X1、Y和L，可以改变化合物作为各种半胱氨酸蛋白酶类型抑制剂的相对选择性，例如半胱氨酸蛋白酶B、K、L和S，可改变，例如获得选择性抑制特定蛋白酶类型或蛋白酶类型组合的抑制剂。
• THE SYNTHESIS OF L-α-AMINONITRILES
  作者：Katsuhiro Kawashiro、Hideyuki Yoshida、Shiro Morimoto

  DOI：10.1246/cl.1976.417

  日期：1976.5.5

  N-o-Nitrophenylsulfenyl(NPS)-l-α-amino acid(alanine, leucine, and phenylalanine) amides were dehydrated in POCl3-pyridine to yield the corresponding NPS-l-α-aminonitriles, which gave the l-α-aminonitrile hydrochlorides by treatment with anhydrous HCl. Optical purity of these nitriles was well retained.

  N-硝基苯磺酰基(NPS)-L-α-氨基酸（丙氨酸、亮氨酸和苯丙氨酸）酰胺在POCl3-吡啶中脱水，得到相应的NPS-L-α-氨基腈，经过无水盐酸处理后得到L-α-氨基腈盐酸盐。这些腈的光学纯度得到了很好保持。