2-amino-2-methyl-N-phenyl-propanamide | 20049-03-0

• 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: 2-amino-2-methyl-N-phenyl-propanamide
• 英文别名: 2-Amino-2-methylpropananilid；DL-α-methylphenyl alanine amide；2-amino-2-methyl-N-phenylpropanamide
• CAS: 20049-03-0
• 化学式: C₁₀H₁₄N₂O
• mdl: MFCD13562611
• 分子量: 178.234
• InChiKey: JAYWADDVMGWPRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-2-methyl-N-phenyl-propanamide 在 lithium aluminium tetrahydride 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以99%的产率得到N-(2-氨基-2-甲基丙基)苯胺
  参考文献：
  名称：

  室温下铜与胺或氨的功能化α-溴甲酰胺的铜催化胺化

  摘要：

  关于烷基胺的合成有一些报道，但是大多数报道的方法不适合于受阻胺的合成。在这项研究中，我们发现铜催化剂可在室温下有效形成拥塞的C-N键。对照实验表明，酰胺铜是关键中间体。此外，当使用手性胺时，以良好的选择性产生了季碳立构中心。

  DOI：

  10.1002/anie.201706293
• 作为产物：
  描述：

  tert-butyl (2-methyl-1-oxo-1-(phenylamino)propan-2-yl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-amino-2-methyl-N-phenyl-propanamide
  参考文献：
  名称：

  中心氨基酸构象受限的二酰胺：设计、合成和生物活性

  摘要：

  以氯虫苯甲酰胺（CHL）为代表的二酰胺类杀虫剂广泛应用于鳞翅目昆虫的防治。为了开发具有新型支架的生物活性二酰胺，我们设计并合成了一系列含有中心氨基酸的二酰胺，以在构象上模拟 CHL。生物测定结果表明，大多数含有 1-氨基环丙烷-1-羧酸的化合物对Mythimna separate和Plutella xylostella表现出优异的杀幼虫效力。经过系统的结构-活性关系研究，1-23被确定为潜在的杀虫剂候选物，其 LC 50值分别为 34.920 mg·L -1和61.992 mg·L -1在P. xylostella上。最后，分子对接揭示了1-23与靶蛋白兰尼碱受体的可能结合模式。

  DOI：

  10.1002/jhet.4443

文献信息

• 3-Carbamoyl-2-Pyridone Derivative
  申请人：Ishizuka Natsuki

  公开号：US20080103139A1

  公开（公告）日：2008-05-01

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R 1 is optionally substituted C1-C8 alkyl and the like; R 2 is C1-C6 alkyl; R 3 is C1-C6 alkyl and the like; or R 2 and R 3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R 4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R 5 is hydrogen and the like; X 1 is a single bond and the like; X 2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of —O—, or —N(R 6 )—, wherein R 6 is hydrogen and the like, and the like; X 3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了具有激动大麻素受体的作用的化合物，其由式（I）表示：其中，R1是可选取的取代的C1-C8烷基等；R2是C1-C6烷基；R3是C1-C6烷基等；或R2和R3共同形成可选取代的5至10个成员的非芳香碳环；R4是氢等；G是由式等所示的基团中选取的基团：其中，R5是氢等；X1是单键等；X2是可选取代的C1-C8烷基，可以被一或两个-O-或-N（R6）-的基团替代，其中R6是氢等；X3是单键等；其药学上可接受的盐或其溶剂，以及制药组合物、治疗特应性皮炎的制剂和抗瘙痒剂，特别是口服和外用的抗瘙痒剂，每种制剂均以所述化合物为活性成分。
• 3-CARBAMOYL-2-PYRIDONE DERIVATIVES
  申请人：ISHIZUKA Natsuki

  公开号：US20120208813A1

  公开（公告）日：2012-08-16

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R 1 , R 2 , R 3 , R 4 , and G are defined as herein, a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了具有激动大麻素受体的活性的化合物，该受体由公式（I）表示：其中R1、R2、R3、R4和G如本文所定义，其药学上可接受的盐或溶剂，以及制备该化合物为活性成分的药物组合物、治疗特应性皮炎的药剂和抗瘙痒剂，尤其是用于口服和外用的抗瘙痒剂。
• 3-CARBAMOYL-2-PYRIDONE DERIVATIVE
  申请人：SHIONOGI & CO., LTD.

  公开号：EP1806342A1

  公开（公告）日：2007-07-11

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R1 is optionally substituted C1-C8 alkyl and the like; R2 is C1-C6 alkyl; R3 is C1-C6 alkyl and the like; or R2 and R3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R5 is hydrogen and the like; X1 is a single bond and the like; X2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of -O-, or -N(R6)-, wherein R6 is hydrogen and the like, and the like; X3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了对大麻素受体具有激动活性的化合物，该受体由式 (I) 表示： 其中 R1 是任选取代的 C1-C8 烷基及类似物；R2 是 C1-C6 烷基；R3 是 C1-C6 烷基及类似物；或 R2 和 R3 一起可形成任选取代的 5 至 10 个成员的非芳香族碳环；R4 是氢及类似物；G 是选自式所示基团及类似物的基团： 其中 R5 是氢和类似物；X1 是单键和类似物；X2 是可被一个或两个基团-O-或-N(R6)-取代的任选取代的 C1-C8 亚烷基，其中 R6 是氢和类似物；X3 是单键和类似物； 其药学上可接受的盐或溶液，以及药物组合物、特应性皮炎治疗剂和止痒剂，尤其是口服和外用的止痒剂，其中每一种都含有上述化合物作为活性成分。
• Chemoselective Peptidomimetic Ligation Using Thioacid Peptides and Aziridine Templates
  作者：Naila Assem、Aditya Natarajan、Andrei K. Yudin

  DOI：10.1021/ja104488d

  日期：2010.8.18

  Chemoselective peptidomimetic ligation has been made possible using thioacid peptides and NH aziridine-terminated amino acids and peptides. In the course of this reaction, a reduced amide bond is incorporated into the backbone of a peptide. This process enables incorporation of reduced cysteine, reduced substituted cysteine, reduced phenylalanine, and reduced alanine. Our method should be adaptable to other unnatural amino acid residues at the ligation site. Experiments aimed at evaluating the chemoselectivity of this process in the presence of competing thiol nucleophiles suggest high specificity at micromolar concentrations. This holds even in the presence of glutathione, which neutralizes xenobiotic electrophiles in cells.
• Synthesis and Structure‐Activity Relationships of <i>N</i> ‐(4‐Benzamidino)‐Oxazolidinones: Potent and Selective Inhibitors of Kallikrein‐Related Peptidase 6
  作者：Elena De Vita、Niels Smits、Helma Hurk、Elizabeth M. Beck、Joanne Hewitt、Gemma Baillie、Emily Russell、Andrew Pannifer、Véronique Hamon、Angus Morrison、Stuart P. McElroy、Philip Jones、Natalia A. Ignatenko、Nikolas Gunkel、Aubry K. Miller

  DOI：10.1002/cmdc.201900536

  日期：2020.1.7

  AbstractKallikrein‐related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high‐throughput screen within the European Lead Factory program. Structure‐guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)‐3‐(4‐carbamimidoylphenyl)‐N‐((S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) and 34 ((5R)‐3‐(6‐carbamimidoylpyridin‐3‐yl)‐N‐((1S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) have single‐digit nanomolar potency against KLK6, with over 25‐fold and 100‐fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32, effectively reduces KLK6‐dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.