N-Acetyl-1-amino-2-methylpropane-2-thiol | 89584-09-8

• 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: N-Acetyl-1-amino-2-methylpropane-2-thiol
• 英文别名: N-(2-mercapto-2-methylpropyl)acetamide；1-(acetylamino)-2-methylpropane-2-thiol；N-(2-methyl-2-sulfanylpropyl)acetamide
• CAS: 89584-09-8
• 化学式: C₆H₁₃NOS
• mdl: MFCD19218725
• 分子量: 147.241
• InChiKey: STVNFNPJRKHUCO-UHFFFAOYSA-N

物化性质

• 沸点：
  283.5±23.0 °C(Predicted)
• 密度：
  0.997±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  30.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-Acetyl-1-amino-2-methylpropane-2-thiol 在 acidic medium 、 sodium nitrite 作用下， 以75%的产率得到1-(acetylamino)-2-methylpropane-2-thionitrite
  参考文献：
  名称：

  New Thionitrites: Synthesis, Stability, and Nitric Oxide Generation

  摘要：

  In order to study the influence of substitutions at the alpha and beta carbon atoms on the stability of the S-NO bond, water-soluble thionitrites RSNO have been synthesized by nitrosation of cysteamine and mercaptoethanol derivatives and characterized. H-1 and C-13 NMR spectroscopies have proven to be excellent probes for the nitrosation of thiols. In water, at physiological pH, the compounds decomposed into nitric oxide NO and the corresponding disulfides. The rate at which NO was released was very sensitive to modifications at the alpha and beta carbon atoms. Tertiary thionitrites were more stable than primary thionitrites. The beta-substituents decreased the rates of decomposition in the following order: OH > NHCOCH3 > NH3+. S-Nitrosocysteamine derivatives were greatly stabilized at low pH. The compounds described here might be convenient and useful as vehicles for spontaneous generation of nitric oxide in biological systems, at rates that can be finely tuned and controlled over a wide range.

  DOI：

  10.1021/jo00102a028
• 作为产物：
  描述：

  1-氨基-2-甲基丙烷-2-硫醇 、 乙酸酐 在 potassium hydroxide 作用下， 以 水 为溶剂， 反应 1.83h， 生成 N-Acetyl-1-amino-2-methylpropane-2-thiol
  参考文献：
  名称：

  [EN] NOVEL CELL-PERMEABLE SUCCINATE COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS DE SUCCINATE PERMÉABLES À TRAVERS LES CELLULES

  摘要：

  本发明提供了新型的细胞可渗透琥珀酸盐和琥珀酸盐的细胞可渗透前体，旨在增加线粒体中的ATP产生。在真核细胞中产生和利用的大部分ATP源自线粒体氧化磷酸化，这是一个高能电子由克雷布氏循环提供的过程。并非所有克雷布氏循环中间体都能轻易渗透到细胞膜，其中之一就是琥珀酸盐。提供新型的细胞可渗透琥珀酸盐可让其通过细胞膜，因此细胞可渗透琥珀酸盐可用于增强线粒体的ATP产出。

  公开号：

  WO2015155231A1

文献信息

• Synthesis, characterization, and protonation of octaethylporphyrin osmium nitrosyl complexes containing axial thiolate ligands - X-ray structures of an alkyl thionitrite (RSNO) and its (OEP)Os(NO)(SR) addition product
  作者：Jonghyuk Lee、Geun-Bae Yi、Douglas R Powell、Masood A Khan、George B Richter-Addo

  DOI：10.1139/v00-168

  日期：2001.5.1

  The (OEP)Os(NO)(SR) compounds (R = Me, Et, i-Pr, t-Bu) have been prepared in 33-48% isolated yields by the formal trans-addition of the precursor alkyl thionitrites (RSNO) across the metal center in (OEP)Os(CO). The nitrosyl thiolate compounds have been characterized by IR,¹H NMR, and UV-vis spectroscopy, and by FAB mass spectrometry. Their IR spectra display bands in the 1751-1755 cm^-1(KBr) range, which is indicative of terminal N-bound NO ligands in this class of compounds. The thiolate-thiol (OEP)Os(NO)(SCH₂CH₂SH) complex has been prepared in 70% isolated yield from the reaction of (OEP)Os(NO)(O-i-C₅H₁₁) with ethane-1,2-dithiol. Nitrosation of the free -SH group in (OEP)Os(NO)(SCH₂CH₂SH) with t-BuONO, followed by reaction with (TTP)Ru(CO) gave [(OEP)Os(NO)](µ-SCH₂CH₂S-S,S')[Ru(NO)(TTP)] in 70% yield by¹H NMR spectroscopy. The (OEP)Os(NO)(SCR'₂CH₂NHC(O)Me) compounds have also been prepared either by an alkoxide-thiolate exchange reaction (for R' = H) or by RSNO addition to (OEP)Os(CO) (for R' = Me). The solid-state molecular structures of the precursor RSNO thionitrite (for R' = Me) and the metalloderivative have been determined by single-crystal X-ray crystallography. Protonation of these (OEP)Os(NO)(SCR'₂CH₂NHC(O)Me) complexes gave the amide-bound [(OEP)Os(NO)(O=C(Me)NHCH₂CR'₂SH)]BF₄derivatives. The latter cationic compounds were also obtained by the sequential reaction of (OEP)Os(CO) with nitrosonium tetrafluoroborate, followed by addition of the amide-thiol reagent. Key words: thionitrite, nitrosothiol, porphyrin, X-ray structure, nitric oxide, osmium.

  (OEP)Os(NO)(SR)化合物（其中R = 甲基，乙基，异丙基，叔丁基）通过前体烷基硫亚硝酸酯（RSNO）在（OEP）Os(CO)金属中心上的形式转加反应，以33-48%的分离收率制备。这些亚硝基硫醇酸盐化合物已通过红外光谱，¹H核磁共振，紫外-可见光谱和FAB质谱进行表征。它们的红外光谱显示在1751-1755 cm^-1（KBr）范围内的吸收峰，表明这类化合物中存在末端N-配位的NO配体。通过（OEP）Os(NO)(O-i-C₅H₁₁)与乙烷-1,2-二硫醇反应，已以70%的分离收率制备了硫醇-硫醇（OEP）Os(NO)(SCH₂CH₂SH)配合物。通过¹H核磁共振光谱，用t-BuONO硝化（OEP）Os(NO)(SCH₂CH₂SH)中的自由-SH基团，然后与（TTP）Ru(CO)反应，得到了[(OEP)Os(NO)](µ-SCH₂CH₂S-S,S')[Ru(NO)(TTP)]，收率为70%。还通过烷氧基-硫醇酸盐交换反应（对于R' = H）或RSNO加成到（OEP）Os(CO)（对于R' = Me）制备了（OEP）Os(NO)(SCR'₂CH₂NHC(O)Me)化合物。通过单晶X射线衍射确定了前体RSNO硫亚硝酸酯（对于R' = Me）和金属衍生物的固态分子结构。这些（OEP）Os(NO)(SCR'₂CH₂NHC(O)Me)配合物的质子化产生了酰胺配位的[(OEP)Os(NO)(O=C(Me)NHCH₂CR'₂SH)]BF₄衍生物。后者阳离子化合物也可通过（OEP）Os(CO)与四氟硼酸亚硝酰盐的顺序反应，然后加入酰胺-硫醇试剂获得。关键词：硫亚硝酸酯，亚硝基硫醇，卟啉，X射线结构，一氧化氮，锇。
• [EN] NOVEL CELL-PERMEABLE SUCCINATE COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS DE SUCCINATE PERMÉABLES À TRAVERS LES CELLULES
  申请人：NEUROVIVE PHARMACEUTICAL AB

  公开号：WO2015155231A1

  公开（公告）日：2015-10-15

  The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.

  本发明提供了新型的细胞可渗透琥珀酸盐和琥珀酸盐的细胞可渗透前体，旨在增加线粒体中的ATP产生。在真核细胞中产生和利用的大部分ATP源自线粒体氧化磷酸化，这是一个高能电子由克雷布氏循环提供的过程。并非所有克雷布氏循环中间体都能轻易渗透到细胞膜，其中之一就是琥珀酸盐。提供新型的细胞可渗透琥珀酸盐可让其通过细胞膜，因此细胞可渗透琥珀酸盐可用于增强线粒体的ATP产出。
• Succinate prodrugs for use in the treatment of lactic acidosis or drug-induced side-effects due to Complex I-related impairment of mitochondrial oxidative phosphorylation
  申请人：NEUROVIVE PHARMACEUTICAL AB

  公开号：US10307389B2

  公开（公告）日：2019-06-04

  The present invention relates to a succinate prodrug for use in the treatment or prevention of lactic acidosis.

  本发明涉及一种用于治疗或预防乳酸中毒的琥珀酸原药。
• Cell-permeable succinate compounds
  申请人：NEUROVIVE PHARMACEUTICAL AB

  公开号：US11147789B2

  公开（公告）日：2021-10-19

  The present invention provides novel cell-permeable succinates and cell permeable precursors of succinateaimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.

  本发明提供了新型细胞渗透性琥珀酸盐和细胞渗透性琥珀酸盐前体，旨在增加线粒体中的 ATP 生成。真核细胞中产生和利用的 ATP 主要来自线粒体氧化磷酸化，这一过程由克雷伯循环提供高能电子。并非所有的克雷伯循环中间产物都能轻易渗透到细胞膜中，琥珀酸就是其中之一。设想提供新型细胞渗透性琥珀酸盐可使其通过细胞膜，因此细胞渗透性琥珀酸盐可用于提高线粒体 ATP 的输出。
• Yi, Geun-Bae; Khan, Masood A.; Powell, Douglas R., Inorganic Chemistry, 1998, vol. 37, # 2, p. 208 - 214
  作者：Yi, Geun-Bae、Khan, Masood A.、Powell, Douglas R.、Richter-Addo, George B.

  DOI：——

  日期：——