S-(p-methoxybenzyl)-β,β-dimethylmercaptopropionic acid | 268219-99-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: S-(p-methoxybenzyl)-β,β-dimethylmercaptopropionic acid
• 英文别名: 3-(4-methoxybenzylthio)-3-methylbutanoic acid；3-[(4-methoxybenzyl)sulfanyl]-3-methylbutanoic acid；3-(4-Methoxy-benzylsulfanyl)-3-methyl-butyric acid；3-[(4-methoxyphenyl)methylsulfanyl]-3-methylbutanoic acid
• CAS: 268219-99-4
• 化学式: C₁₃H₁₈O₃S
• 分子量: 254.35
• InChiKey: VLSLXZFZXHZCHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  S-(p-methoxybenzyl)-β,β-dimethylmercaptopropionic acid 在 草酰氯 、 三氟甲磺酸 、 苯甲醚 、 三氟乙酸 、 肼 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  ヒドラジドを製造するための改善されたプロセス

  摘要：

  要解决的问题：提供一种改进的合成方法，用于从双肼和酰氯制备酰肼。解决方案：公开了一种从双肼和酰氯制备酰肼的方法，包括以下步骤：(a)在低温下制备搅拌均匀的悬浮液，其中包括双肼和惰性溶剂；以及(b)连续向悬浮液中添加酰氯。该方法避免或限制了不良的双肼产物的生成。该方法用于制备3-甲基-3-巯基丁酸酰肼，这是一种用于将卡利基霉素与单克隆抗体连接的分子。所选图纸：无

  公开号：

  JP2016026219A
• 作为产物：
  描述：

  3,3-二甲基丙烯酸甲酯 在 四丁基氟化铵 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 甲醇 为溶剂， 生成 S-(p-methoxybenzyl)-β,β-dimethylmercaptopropionic acid
  参考文献：
  名称：

  [EN] INTERMEDIATES AND METHODS FOR SYNTHESIZING CALICHEAMICIN DERIVATIVES
  [FR] INTERMÉDIAIRES ET PROCÉDÉS DE SYNTHÈSE DE DÉRIVÉS DE LA CALICHÉAMICINE

  摘要：

  本发明涉及式(I)的中间体以及合成和纯化卡利奇阿霉素衍生物的方法。

  公开号：

  WO2015063680A1

文献信息

• [EN] CALICHEAMICIN DERIVATIVES AND ANTIBODY DRUG CONJUGATES THEREOF<br/>[FR] DÉRIVÉS DE CALICHÉAMICINE ET CONJUGUÉS ANTICORPS-MÉDICAMENTS DE CEUX-CI
  申请人：PFIZER

  公开号：WO2018138591A1

  公开（公告）日：2018-08-02

  The present invention is directed to novel calicheamicin derivatives useful as payloads in antibody-drug-conjugates (ADC's), and to payload-linker compounds and ADC compounds comprising the same; to pharmaceutical compositions comprising the same and to methods for using the same to treat pathological conditions such as cancer.

  本发明涉及新型calicheamicin衍生物，用作抗体-药物偶联物（ADC）的有效载荷，以及包含相同有效载荷-连接剂化合物和ADC化合物；涉及包含它们的药物组合物以及使用它们治疗诸如癌症等病理状态的方法。
• Improved processes for making hydrazides
  申请人：Wyeth LLC

  公开号：EP2465541A1

  公开（公告）日：2012-06-20

  A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.

  本发明公开了一种用肼和酰基氯制备肼的方法，该方法包括以下步骤：(a) 在低温下制备由肼和惰性溶剂组成的搅拌基本均匀的浆料；(b) 向所述浆料中连续加入酰基氯。该方法可避免或限制产生不需要的双肼副产物。该方法可用于制备 3-甲基-3-巯基丁酸酰肼，这是一种用于连接卡利昔明和单克隆抗体的分子。
• Intermediates and methods for synthesizing calicheamicin derivatives
  申请人：PFIZER INC.

  公开号：US10508081B2

  公开（公告）日：2019-12-17

  The present invention relates to intermediates of Formula I and to methods of synthesizing and purifying calicheamicin derivatives.

  本发明涉及式 I 的中间体 以及合成和纯化卡利卡明衍生物的方法。
• A Study of the Relationship between Biological Activity and Prolyl Amide Isomer Geometry in Oxytocin Using 5-<i>tert</i>-Butylproline To Augment the Cys⁶-Pro⁷ Amide <i>Cis</i>-Isomer Population
  作者：Laurent Bélec、Jirina Slaninova、William D. Lubell

  DOI：10.1021/jm990090m

  日期：2000.4.1

  Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butyl-proline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both peptides maintained the pharmacophore characteristics responsible for signal transfer evoking the same maximal response as oxytocin in the single-dose procedure and exhibiting partial agonistic activity in the cumulative dose-response procedure. Although [dPen(1)]oxytocin exhibited inhibitory as well as partial agonistic activity, [dPen(1),5-t-BuPro(7)]oxytocin exhibited only inhibitory potency with a similar in vitro pA(2) value of 7.50 in the absence of magnesium. In the presence of magnesium, [dPen(1),5-t-BuPro7]oxytocin exhibited stronger inhibitory potency than [dPen(1)]oxytocin and no partial agonism. Assignment of the proton signals for the 5-tert-butylprolyl amide cis- and trans-isomers by two-dimensional NMR experiments in water indicated that the Cys(6)-Pro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured respectively at 35%, 33%, and 20% in the 5-tert-butylproline(7) analogues of oxytocin, [Mpa(1)]oxytocin and [dPen(1)]oxytocin. Although caution must be taken when relating the increase in cis-isomer population with an influence on biological activity in [5-t-BuPro7(])oxytocin analogues, the synthesis and evaluation of analogues 1-3 have provided additional evidence that can be used to support the hypothesis that the prolyl amide cis-isomer may favor antagonism and the trans-isomer is necessary for agonist activity.
• EP2155258B1
  申请人：——

  公开号：EP2155258B1

  公开（公告）日：2017-08-16