(4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid

• 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: (4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid
• 英文别名: (4R)-1-(tert-butoxycarbonyl)-4-hydroxyproline；N-tert-butoxycarbonyl-(4R)-4-hydroxyproline；Boc-Hyp-OH；(4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• 化学式: C₁₀H₁₇NO₅
• 分子量: 231.249
• InChiKey: BENKAPCDIOILGV-ULUSZKPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 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：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 在 盐酸 、 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 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-) 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 23.33h， 生成 1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  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.

  DOI：

  10.1021/jm201533b

文献信息

• Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition
  作者：Joseph T. Madak、Christine R. Cuthbertson、Wenmin Chen、Hollis D. Showalter、Nouri Neamati

  DOI：10.1002/chem.201702999

  日期：2017.10.9

  Brequinar, a potent dihydroorotate dehydrogenase (DHODH) inhibitor, has been evaluated in multiple clinical trials as a potential treatment for cancer. To further understand brequinar‐based DHODH inhibition and DHODH′s therapeutic relevance in cancer, we have developed novel brequinar‐based probes. We disclose a 16‐step convergent synthesis of the first brequinar‐PROTAC and a four‐step approach towards

  Brequinar是一种有效的二氢乳清酸脱氢酶（DHODH）抑制剂，已在多项临床试验中评估为潜在的癌症治疗方法。为了进一步了解基于臀肌的DHODH抑制作用和DHODH在癌症中的治疗意义，我们开发了新型的基于臀肌的探针。我们公开了第一个brequinar-PROTAC的16个步骤的收敛合成，以及第一个线粒体定向的brequinar探针的四个步骤的方法。在菌落形成试验中，布雷塔那的PROTAC和线粒体定向探针均具有比布雷库那更好的细胞毒性。
• Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes
  作者：Kay Merkens、Francisco José Aguilar Troyano、Jonas Djossou、Adrián Gómez‐Suárez

  DOI：10.1002/adsc.202000300

  日期：2020.6.15

  Unnatural amino acids (UAAs) are key building blocks with widespread application across several scientific fields. Therefore, it is highly attractive to develop straightforward and simple methodologies capable of granting quick access to these species. Herein we report a light‐mediated protocol for the synthesis of UAA via radical decarboxylative processes. This methodology, which employs readily available

  非天然氨基酸（UAA）是关键组成部分，已在多个科学领域中得到广泛应用。因此，开发能够允许快速访问这些物种的简单明了的方法论具有很高的吸引力。本文中，我们报告了一种通过自由基脱羧过程合成UAA的光介导协议。这种方法采用了容易获得的丰富原料，例如羧酸和α-酮酸，在非常温和的反应条件下进行，显示出很高的官能团耐受性。此外，自由基反应的产物可以很容易地衍生化，从而可以快速获得复杂的UAA。
• Hepatitis C Virus Inhibitors
  申请人：Sin Ny

  公开号：US20080119461A1

  公开（公告）日：2008-05-22

  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.

  抑制丙型肝炎病毒的抑制剂具有一般公式。包含这些化合物的组合物以及使用这些化合物抑制HCV的方法也被披露。
• HCV NS-3 serine protease inhibitors
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1881002A1

  公开（公告）日：2008-01-23

  HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, of formula: wherein A is

  HCV抑制剂，包含这些化合物作为活性成分的组合物，以及制备这些化合物的方法，其化学式为：其中A是
• Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
  申请人：Akritopoulou-Zanze Irini

  公开号：US20050215603A1

  公开（公告）日：2005-09-29

  The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, obesity, atherosclerosis, and various immunomodulatory diseases.

  本发明涉及一种化合物，其化学式为(I)，能够抑制二肽基肽酶IV（DPP-IV），并且可用于预防或治疗糖尿病，特别是2型糖尿病，以及高血糖、X综合征、高胰岛素血症、肥胖、动脉粥样硬化和各种免疫调节性疾病。