2-methylazetidine-1,2-dicarboxylic acid 1-tert-butyl ester | 1363402-35-0

• 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-methylazetidine-1,2-dicarboxylic acid 1-tert-butyl ester
• 英文别名: Boc-(S)-(αMe)Aze-OH；(S)-2-methyl-azetidine-1,2-dicarboxylic acid 1-tert-butyl ester；(2S)-1-[(tert-Butoxy)carbonyl]-2-methylazetidine-2-carboxylic acid；(2S)-2-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-2-carboxylic acid
• CAS: 1363402-35-0
• 化学式: C₁₀H₁₇NO₄
• 分子量: 215.249
• InChiKey: HFEGSFBKYUXELG-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-methylazetidine-1,2-dicarboxylic acid 1-tert-butyl ester 、 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 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以0.163 g的产率得到Boc-[(S)-(αMe)Aze-(S)-Ala]₃-OMe
  参考文献：
  名称：

  一种新的肽构象：γ-弯曲带

  摘要：

  与广泛研究的肽β弯曲带与其原型3 10螺旋构象之间的关系不同，较窄的γ弯曲带与其规则γ螺旋对应物之间的对应关系仍有待研究，因为后者的3D结构尚未通过实验验证。在本文中，我们描述了使用X射线衍射和FT-IR吸收，电子CD和2D-NMR光谱学对γ弯曲带状构象进行首次表征的结果，无论是在晶体状态还是在溶液中。合成的适当的一组的基础上，（同型手性的，连续的二肽的低聚物小号）-Ala和已知γ-弯曲诱导剂，ç α -tetrasubstituted，ñ烷基化α氨基酸残基（小号） - c ^ α -甲基-氮杂环丁烷羧酸。

  DOI：

  10.1039/c8ob02279h
• 作为产物：
  描述：

  Tert-butyl 1-benzyl-2-methylazetidine-2-carboxylate 在 硫酸 、 20 % Pd(OH)2/C 、 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 60.0 ℃ 、800.01 kPa 条件下， 反应 65.0h， 生成 2-methylazetidine-1,2-dicarboxylic acid 1-tert-butyl ester
  参考文献：
  名称：

  Practical preparation of enantiopure 2-methyl-azetidine-2-carboxylic acid; a γ-turn promoter

  摘要：

  A robust and practical synthesis of each enantiomer of 2-methyl-azetidine-2-carboxylic acid, based on the use of (S)-phenylglycinol as resolving agent, is described. This synthesis affords practical quantities of this quaternary amino acid suitably N- and C-protected for use in further peptide coupling. Synthetic highlights include the formation of the azetidine ring by intramolecular alkylation and the facile separation of the diastereoisomeric amides derived from phenylglycinol. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.05.006

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。
• Discovery and Optimization of an Azetidine Chemical Series As a Free Fatty Acid Receptor 2 (FFA2) Antagonist: From Hit to Clinic
  作者：Mathieu Pizzonero、Sonia Dupont、Marielle Babel、Stéphane Beaumont、Natacha Bienvenu、Roland Blanqué、Laëtitia Cherel、Thierry Christophe、Benedetta Crescenzi、Elsa De Lemos、Philippe Delerive、Pierre Deprez、Steve De Vos、Fatoumata Djata、Stephen Fletcher、Sabrina Kopiejewski、Christelle L’Ebraly、Jean-Michel Lefrançois、Stéphanie Lavazais、Murielle Manioc、Luc Nelles、Line Oste、Denis Polancec、Vanessa Quénéhen、Florilène Soulas、Nicolas Triballeau、Ellen M. van der Aar、Nick Vandeghinste、Emanuelle Wakselman、Reginald Brys、Laurent Saniere

  DOI：10.1021/jm5012885

  日期：2014.12.11

  FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic.
• US6645939B1
  申请人：——

  公开号：US6645939B1

  公开（公告）日：2003-11-11
• US8759334B2
  申请人：——

  公开号：US8759334B2

  公开（公告）日：2014-06-24