(3S,4R)-3-hydroxy-4-(methylthiomethyl)pyrrolidine | 915227-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3S,4R)-3-hydroxy-4-(methylthiomethyl)pyrrolidine
• 英文别名: (3S,4R)-3-hydroxy-4-(methylthiomethyl)-pyrrolidine；(3S,4R)-3-hydroxy-4-methylthiomethylpyrrolidine；(3S,4R)-4-(methylsulfanylmethyl)pyrrolidin-3-ol
• CAS: 915227-51-9
• 化学式: C₆H₁₃NOS
• 分子量: 147.241
• InChiKey: ISXICUZGXJZCEJ-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,4R)-3-hydroxy-4-(methylthiomethyl)pyrrolidine 、 N-benzoyl-N-(7-(2-oxoethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzamide 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  WO2006/123953

  摘要：

  公开号：
• 作为产物：
  描述：

  (3S,4S)-4-(羟甲基)吡咯烷-3-醇 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 (3S,4R)-3-hydroxy-4-(methylthiomethyl)pyrrolidine
  参考文献：
  名称：

  Tight binding enantiomers of pre-clinical drug candidates

  摘要：

  MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.059

文献信息

• [EN] IMPROVED METHOD FOR PREPARING 3-HYDROXY-4-HYDROXYMETHYL-PYRROLIDINE COMPOUNDS<br/>[FR] PROCEDE AMELIORE DE PREPARATION DE COMPOSES 3-HYDROXY-4-HYDROXYMETHYL-PYRROLIDINE
  申请人：IND RES LTD

  公开号：WO2005118532A1

  公开（公告）日：2005-12-15

  A process for preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (I), or (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (Ia) involving, as a key step, the enzyme-catalysed enantioselective hydrolysis of a racemic 3,4-trans-disubstituted pyrrolidinone compound of formula (II).

  一种制备式（I）化合物（（3R,4R）-3-羟基-4-羟甲基吡咯烷）或式（Ia）化合物（（3S,4S）-3-羟基-4-羟甲基吡咯烷）的方法，其中关键步骤涉及以酶催化的对称选择性水解3,4-反式二取代吡咯烷酮化合物（II）。
• Inhibitors of nucleoside phosphorylases and nucleosidases
  申请人：Evans Gary Brian

  公开号：US20090233948A1

  公开（公告）日：2009-09-17

  The present invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

  本发明涉及通式（I）的化合物，其为嘌呤核苷酸磷酸酯酶（PNP）、嘌呤磷酸核糖转移酶（PPRT）、5'-甲基硫腺苷磷酸酶（MTAP）、5'-甲基硫腺苷核苷酸酶（MTAN）和/或核苷酸水解酶（NH）的抑制剂。本发明还涉及使用这些化合物治疗包括癌症、细菌感染、原虫感染和T细胞介导疾病在内的疾病和感染，并含有这些化合物的制药组合物。
• Method for Preparing 3-Hydroxy-4-Hydroxymethyl-Pyrrolidine Compounds
  申请人：Lenz Dirk Henning

  公开号：US20080280334A1

  公开（公告）日：2008-11-13

  A process is disclosed for preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (I), or (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (Ia) involving, as a key step, the enzyme-catalysed enantioselective hydrolysis of a racemic 3,4-trans-disubstituted pyrrolidinone compound of formula (II).

  本发明揭示了一种制备式(I)化合物(3R,4R)-3-羟基-4-羟甲基吡咯烷或式(Ia)化合物(3S,4S)-3-羟基-4-羟甲基吡咯烷的方法，其中的关键步骤是通过酶催化的对式(II)的外消旋3,4-顺式取代吡咯烷化合物的拆分，实现对映选择性水解。
• Method for preparing 3-hydroxy-4-hydroxymethyl-pyrrolidine compounds
  申请人：Industrial Research Limited

  公开号：US08183019B2

  公开（公告）日：2012-05-22

  A process is disclosed for preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (I), or (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (Ia) involving, as a key step, the enzyme-catalysed enantioselective hydrolysis of a racemic 3,4-trans-disubstituted pyrrolidinone compound of formula (II).

  本发明揭示了一种制备（3R,4R）-3-羟基-4-羟甲基吡咯烷（式I化合物）或（3S,4S）-3-羟基-4-羟甲基吡咯烷（式Ia化合物）的方法，其中包括酶催化对式（II）的外消旋3,4-顺式取代吡咯烷化合物的对映选择性水解作为关键步骤。
• Residence Times for Femtomolar and Picomolar Inhibitors of MTANs
  作者：Morais Brown、Peter C. Tyler、Vern L. Schramm

  DOI：10.1021/acs.biochem.3c00145

  日期：2023.6.6

  nucleosidases (MTANs) catalyze the hydrolysis of 5′-substituted adenosines to form adenine and 5-substituted ribose. Escherichia coli MTAN (EcMTAN) and Helicobacter pylori MTAN (HpMTAN) form late and early transition states, respectively. Transition state analogues designed for the late transition state bind with fM to pM affinity to both classes of MTANs. Here, we compare the residence times (off-rates)

  5'-甲硫腺苷核苷酶 (MTAN) 催化 5'-取代腺苷水解形成腺嘌呤和 5-取代核糖。大肠杆菌MTAN ( Ec MTAN) 和幽门螺杆菌MTAN ( Hp MTAN) 分别形成晚期和早期过渡态。专为晚期过渡态设计的过渡态类似物与两类 MTAN 具有 fM 至 pM 亲和力。在这里，我们使用五个 5' 取代的 DADMe-ImmA 过渡态类似物，将Hp MTAN 和Ec MTAN的停留时间（解离速率）与平衡解离常数进行比较。抑制剂与Ec MTAN 的解离速度比与Hp的解离速度慢几个数量级MTAN。例如，尽管结构相似，但Ec MTAN-HTDIA 复合物的释放速率最慢（t 1/2 = 56 小时），而与Hp MTAN 的相同复合物的释放速率为t 1/2 = 0.3 小时以及这些酶的催化位点。其他抑制剂也揭示了停留时间和平衡解离常数之间的脱节。停留时间与药理功效相关；因此，解离速率的实验分析