2-benzyl-2-methoxycarbonylazetidine | 681456-91-7

• 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: 2-benzyl-2-methoxycarbonylazetidine
• 英文别名: Methyl 2-(phenylmethyl)-2-azetidinecarboxylate；methyl 2-benzylazetidine-2-carboxylate
• CAS: 681456-91-7
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: JGYSYDWOELNUTP-UHFFFAOYSA-N

物化性质

• 沸点：
  292.5±35.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-benzyl-2-methoxycarbonylazetidine 在 sodium hydroxide 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 、 methyloxirane 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-[(2-benzyl-1-phenylmethoxycarbonylazetidine-2-carbonyl)amino]propanoic acid
  参考文献：
  名称：

  From 1-Acyl-β-lactam Human Cytomegalovirus Protease Inhibitors to 1-Benzyloxycarbonylazetidines with Improved Antiviral Activity. A Straightforward Approach To Convert Covalent to Noncovalent Inhibitors

  摘要：

  Starting from the structure of known beta-lactam covalent human cytomegalovirus (HCMV) protease inhibitors and from the knowledge of the residues implicated in the active site of this enzyme, we designed a series of phenylalanine-derived 2-azetidinones bearing a 4-carboxylate moiety that could be apt for additional interactions with the guanidine group of the Arg165/ Arg166 residues of the viral protease. Some compounds within this series showed anti-HCMV activity at 10-50 mu M, but rather high toxicity. The presence of aromatic 1-acyl groups and a certain hydrophobic character in the region of the 4-carboxylate were stringent requirements for anti-HCMV activity. To go a step ahead into the search for effective HCMV medicines, we then envisaged a series of noncovalent inhibitors by simple deletion of the carbonyl group in the beta-lactam derivatives to provide the corresponding azetidines. This led to low micromolar inhibitors of HCMV replication, with 17 and 27 being particularly promising lead compounds for further investigation, although their toxicity still needs to be lowered.

  DOI：

  10.1021/jm0492812

文献信息

• [EN] AZETIDINE DERIVATIVES USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS D'AZÉTIDINE UTILES POUR LE TRAITEMENT DE MALADIES MÉTABOLIQUES ET INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2012098033A1

  公开（公告）日：2012-07-26

  Compounds are disclosed that have a formula represented by the following: These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example inflammatory conditions, infectious diseases, autoimmune diseases, diseases involving impairment of immune cell functions, cardiometabolic diseases, and/or proliferative diseases.

  披露了具有以下表示的公式的化合物：这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如炎症性疾病、传染病、自身免疫疾病、涉及免疫细胞功能受损的疾病、心脏代谢疾病和/或增殖性疾病，举例不限。
• NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES
  申请人：Sanière Laurent Raymond Maurice

  公开号：US20130303515A1

  公开（公告）日：2013-11-14

  Compounds are disclosed that have a formula represented by the following: These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example inflammatory conditions, infectious diseases, autoimmune diseases, diseases involving impairment of immune cell functions, cardiometabolic diseases, and/or proliferative diseases.

  公开了具有以下式子表示的化合物：这些化合物可以制备成药物组合物，并可用于哺乳动物，包括人类的预防和治疗，例如炎症性疾病、传染病、自身免疫疾病、涉及免疫细胞功能受损的疾病、心脏代谢疾病和/或增殖性疾病等。
• Synthesis and SAR studies on azetidine-containing dipeptides as HCMV inhibitors
  作者：Paula Pérez-Faginas、M. Teresa Aranda、M. Teresa García-López、Robert Snoeck、Graciela Andrei、Jan Balzarini、Rosario González-Muñiz

  DOI：10.1016/j.bmc.2010.12.052

  日期：2011.2

  SAR studies on an azetidine-containing dipeptide prototype inhibitor of HCMV are described. Three series of structurally modified analogues, involving substitutions at the N- and C-terminus, and at the C-terminal side-chain were synthesized and evaluated for antiviral activity. Aliphatic or no substituents at the C-carboxamide group, an aliphatic C-terminal side-chain, as well as a benzyloxycarbonyl moiety at the N-terminus were absolute requirements for anti-HCMV activity. The conformational restriction induced by the 2-azetidine residue into the dipeptide derivatives, identified by H-1 NMR as a gamma-type reverse turn, seems to have influence on the activity of these molecules. (C) 2010 Elsevier Ltd. All rights reserved.
• Further Evidence for 2-Alkyl-2-carboxyazetidines as γ-Turn Inducers
  作者：José Luis Baeza、Guillermo Gerona-Navarro、Kevin Thompson、M. Jesús Pérez de Vega、Lourdes Infantes、M. Teresa García-López、Rosario González-Muñiz、Mercedes Martín-Martínez

  DOI：10.1021/jo901712x

  日期：2009.11.6

  Reverse turns, it common motif in proteins and peptides, have attracted attention due to their relevance in it Wide variety of biological processes. In in attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines, and incorporated them into the i + 1 position of model tetrapeptides, where they have shown it tendency to induce gamma-turns However, to ascertain the general utility of these restricted amino acids its gamma-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently Substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and Subjected to it thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce gamma-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.
• US8759334B2
  申请人：——

  公开号：US8759334B2

  公开（公告）日：2014-06-24