Boc-(2s,4r)-4-苄基-吡咯烷-2-羧酸 | 153074-95-4

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 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
• 中文名称: Boc-(2s,4r)-4-苄基-吡咯烷-2-羧酸
• 中文别名: (2S,4R)-4-苄基-1-(叔丁氧羰基)吡咯烷-2-羧酸；(2S,4R)-4-苯甲基-1-(叔-丁氧羰基)吡咯烷-2-羧酸
• 英文名称: (2S,4R)-4-benzyl-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4R)-4-benzyl-N-tert-butyloxycarbonylproline；(2S,4R)-1-(tert-butoxycarbonyl)-4-benzylpyrrolidine-2-carboxylic acid；(2S,4R)-4-benzyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 153074-95-4
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: JPNHKKRLLDYCIZ-KGLIPLIRSA-N

物化性质

• 熔点：
  100-102℃
• 沸点：
  447.9±38.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  Boc-(2s,4r)-4-苄基-吡咯烷-2-羧酸 在 哌啶 、 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 (2S,4R)-1-[(S)-5-({Amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl}-amino)-2-phenylacetylamino-pentanoyl]-4-benzyl-pyrrolidine-2-carboxylic acid benzylamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of proline based melanocortin receptor ligands

  摘要：

  A series of proline based melanocortin ligands has been developed on the basis of initial piperazine leads by using a more conformationally rigid scaffold. A number of these novel ligands showed significant binding affinity for MC3 and MC4 receptors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.120
• 作为产物：
  描述：

  L-羟基脯氨酸 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium tetrahydroborate 、 TEA 、 三氯异氰尿酸 、 potassium tert-butylate 、 四丁基氟化铵 、 氢气 、 镍 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， -20.0~45.0 ℃ 、101.33 kPa 条件下， 反应 68.83h， 生成 Boc-(2s,4r)-4-苄基-吡咯烷-2-羧酸
  参考文献：
  名称：

  不对称氢化，用于合成Boc保护的4-烷基脯氨醇和脯氨酸。

  摘要：

  4-取代的脯氨醇及其相应的脯氨酸在肽，拟肽和天然产物中的用途促使研究人员寻找新的有效制备方法。在这里，我们报告了一种通过不对称加氢策略合成Boc保护的4-烷基脯氨醇和脯氨酸的一般方法。中间体外环烯烃通过与酮6的维蒂希型反应制备，并进行羟基还原和空间定向还原。事实证明，Crabtree催化剂（Ir [COD] PyPCy（3）PF（6））在非对映选择性氢化中非常有效，可得到反式取代的吡咯烷（9）。在用阮内镍进行异质氢化中也观察到了良好的面部选择性，从而获得了顺式取代的吡咯烷（11）。运用这种策略，

  DOI：

  10.1021/jo034214l

文献信息

• Hepatitis C virus inhibitors
  申请人：Sin Ny

  公开号：US20080152619A1

  公开（公告）日：2008-06-26

  Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

  披萨病毒抑制剂的一般公式已被揭示。还揭示了包含该化合物的组合物以及使用该化合物抑制HCV的方法。
• Sphingosine-1-Phosphate Receptor Antagonists
  申请人：Ibrahim Mohamed Abdulkader

  公开号：US20110288076A1

  公开（公告）日：2011-11-24

  This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particularly, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor antagonists.

  本公开涉及鞘氨醇-1-磷酸（S1P）受体拮抗剂，包括含有S1P受体拮抗剂的组合物，以及使用和制备S1P受体拮抗剂的方法。特别地，本公开涉及鞘氨醇-1-磷酸1（S1P1）受体拮抗剂，包括含有S1P1受体拮抗剂的组合物，以及使用S1P1受体拮抗剂的方法，例如用于治疗癌症，以及制备S1P1受体拮抗剂的方法。
• Acetanilide sphingosine-1-phosphate receptor antagonists
  申请人：Ibrahim Mohamed Abdulkader

  公开号：US08791102B2

  公开（公告）日：2014-07-29

  This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particular, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor antagonists.

  本披露涉及鞘氨醇-1-磷酸（S1P）受体拮抗剂，包括含有S1P受体拮抗剂的组合物以及使用S1P受体拮抗剂的方法和制备S1P受体拮抗剂的过程。特别是，本披露涉及鞘氨醇-1-磷酸1（S1P1）受体拮抗剂，包括含有S1P1受体拮抗剂的组合物以及使用S1P1受体拮抗剂的方法，例如用于癌症治疗，并制备S1P1受体拮抗剂的过程。
• Discovery of Potent and Specific Dihydroisoxazole Inhibitors of Human Transglutaminase 2
  作者：Cornelius Klöck、Zachary Herrera、Megan Albertelli、Chaitan Khosla

  DOI：10.1021/jm501145a

  日期：2014.11.13

  Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes the posttranslational modification of glutamine residues on protein or peptide substrates. A growing body of literature has implicated aberrantly regulated activity of TG2 in the pathogenesis of various human inflammatory, fibrotic, and other diseases. Taken together with the fact that TG2 knockout mice are developmentally and reproductively normal, there is growing interest in the potential use of TG2 inhibitors in the treatment of these conditions. Targeted-covalent inhibitors based on the weakly electrophilic 3-bromo-4,5-dihydroisoxazole (DHI) scaffold have been widely used to study TG2 biology and are well tolerated in vivo, but these compounds have only modest potency, and their selectivity toward other transglutaminase homologues is largely unknown. In the present work, we first profiled the selectivity of existing inhibitors against the most pertinent TG isoforms (TG1, TG3, and FXIIIa). Significant cross-reactivity of these small molecules with TG1 was observed. Structure-activity and -selectivity analyses led to the identification of modifications that improved potency and isoform selectivity. Preliminary pharmacokinetic analysis of the most promising analogues was also undertaken. Our new data provides a clear basis for the rational selection of dihydroisoxazole inhibitors as tools for in vivo biological investigation.
• Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists
  作者：Mohamed A. Ibrahim、Henry W. B. Johnson、Joon Won Jeong、Gary L. Lewis、Xian Shi、Robin T. Noguchi、Matthew Williams、James W. Leahy、John M. Nuss、John Woolfrey、Monica Banica、Frauke Bentzien、Yu-Chien Chou、Anna Gibson、Nathan Heald、Peter Lamb、Larry Mattheakis、David Matthews、Aaron Shipway、Xiang Wu、WenTao Zhang、Sihong Zhou、Geetha Shankar

  DOI：10.1021/jm201533b

  日期：2012.2.9

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.