1-{[(ethylthio)carbonyl]oxy}ethyl pivalate | 467229-23-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代缩醛
• 英文名称: 1-{[(ethylthio)carbonyl]oxy}ethyl pivalate
• 英文别名: 1-{[(ethylthio)carbonyl]oxy} pivalate；1-{[(Ethylsulfanyl)carbonyl]oxy}ethyl 2,2-dimethylpropanoate；1-ethylsulfanylcarbonyloxyethyl 2,2-dimethylpropanoate
• CAS: 467229-23-8
• 化学式: C₁₀H₁₈O₄S
• 分子量: 234.317
• InChiKey: YHJIGVXDIDHNJX-UHFFFAOYSA-N

物化性质

• 沸点：
  289.0±42.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{[(ethylthio)carbonyl]oxy}ethyl pivalate 在 过氧乙酸 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 反应 3.25h， 生成 isopropyl 6-diazo-5-oxo-2-(((1-(pivaloyloxy)ethoxy)-carbonyl)amino)hexanoate
  参考文献：
  名称：

  N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders

  摘要：

  Aberrant excitatory neurotransmission associated with overproduction of glutamate has been implicated in the development of HIV-associated neurocognitive disorders (HAND). The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 14) attenuates glutamate synthesis in HIV-infected microglia/macrophages, offering therapeutic potential for HAND. We show that 14 prevents manifestation of spatial memory deficits in chimeric EcoHIV-infected mice, a model of HAND. 14 is not clinically available, however, because its development was hampered by peripheral toxicities. We describe the synthesis of several substituted N-(pivaloyloxy)alkoxy-carbonyl prodrugs of 14 designed to circulate inert in plasma and be taken up and biotransformed to 14 in the brain. The lead prodrug, isopropyl 6-diazo-5-oxo-2-(((phenyl(pivaloyloxy)methoxy)carbonyl)amino)hexanoate (13d), was stable in swine and human plasma but liberated 14 in swine brain homogenate. When dosed systemically in swine, 13d provided a 15-fold enhanced CSF-to-plasma ratio and a 9-fold enhanced brain-to-plasma ratio relative to 14, opening a possible clinical path for the treatment of HAND.

  DOI：

  10.1021/acs.jmedchem.7b00966
• 作为产物：
  描述：

  O-(1-chloroethyl) S-ethyl carbonothioate 在 18-冠醚-6 、 四丁基硫酸氢铵 、 碳酸氢钠 、 sodium iodide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 148.5h， 生成 1-{[(ethylthio)carbonyl]oxy}ethyl pivalate
  参考文献：
  名称：

  CYCLOALKYL-SUBSTITUTED IMIDAZOLE DERIVATIVE

  摘要：

  公开号：

  EP2548871B1

文献信息

• Synthesis, bioconversion, pharmacokinetic and pharmacodynamic evaluation of N-isopropyl-oxy-carbonyloxymethyl prodrugs of CZh-226, a potent and selective PAK4 inhibitor
  作者：Jing Guo、Tingting Wang、Tianxiao Wu、Kehan Zhang、Wenbo Yin、Mingyue Zhu、Yu Pang、Chenzhou Hao、Zhonggui He、Maosheng Cheng、Yang Liu、Jiang Zheng、Jingkai Gu、Dongmei Zhao

  DOI：10.1016/j.ejmech.2019.111878

  日期：2020.1

  We have previously disclosed compound 3 (CZh-226), a potent and selective PAK4 inhibitor, but its development was delayed due to poor oral pharmacokinetics. In an attempt to improve this issue, we synthesised a series of prodrugs by masking its terminal nitrogen of the piperazine moiety. Most synthesised prodrugs of 3 have low or no inhibition of PAK4 activity. The stability of synthetic prodrugs was

  我们之前已经披露了化合物3（CZh-226），一种有效的选择性PAK4抑制剂，但是由于不良的口服药代动力学，其开发被推迟了。为了改善这个问题，我们通过掩盖哌嗪部分的末端氮合成了一系列前药。大多数合成的3的前药对PAK4活性的抑制作用很小或没有。在PBS，SGF，SIF，大鼠血浆和肝S9级分中评估了合成前药的稳定性。其中，前药19不仅在酸性和中性条件下均稳定，而且可以在大鼠血浆和肝脏S9组分中迅速转化为母体药物3。在大鼠中观察到了这种有效转化为母体药物3的情况，与直接给药相比，其暴露量更高。当口服剂量为每日25和50 mg / kg时，
• Prodrugs of 9-aminomethyl tetracycline compounds
  申请人：Ohemeng Kwasi

  公开号：US20050137174A1

  公开（公告）日：2005-06-23

  The invention pertains to prodrugs of 9-aminomethyl substituted tetracycline compounds, methods of using the compounds, and pharmaceutical compositions containing them.

  本发明涉及9-氨甲基取代四环素化合物的前药、使用该化合物的方法以及包含它们的制药组合物。
• PRODRUGS OF 9-AMINOMETHYL TETRACYCLINE COMPOUNDS
  申请人：Amoo Victor

  公开号：US20100249076A1

  公开（公告）日：2010-09-30

  The invention pertains to prodrugs of 9-aminomethyl substituted tetracycline compounds, methods of using the compounds, and pharmaceutical compositions containing them.

  本发明涉及9-氨甲基取代四环素化合物的前药，使用该化合物的方法以及含有它们的制药组合物。
• Cycloalkyl-Substituted Imidazole Derivative
  申请人：Nagata Tsutomu

  公开号：US20130022587A1

  公开（公告）日：2013-01-24

  A compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof, wherein A represents a C3 to C12 cycloalkyl group which may be substituted by one to three selected from a fluoro group, a hydroxy group, a C1 to C6 alkyl group, etc; R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a fluoro group, or a C1 to C6 alkyl group; R 4 represents a hydrogen atom or a prodrug group; and Y represents —CH 2 —CHR 5 —CH 2 —NHR 6 (wherein R 5 represents a hydrogen atom, a C1 to C6 alkyl group, or a C1 to C6 alkoxy group, and R 6 represents a hydrogen atom or a prodrug group), or the like exhibits excellent TAFIa inhibitory activity and is useful as a therapeutic drug for myocardial infarction, angina pectoris, acute coronary syndrome, cerebral infarction, deep vein thrombosis, pulmonary embolism, and the like.

  以下是通式（I）所代表的化合物或其药学上可接受的盐，其中A代表一个C3到C12的环烷基，该环烷基可以被一个到三个选自氟基、羟基、C1到C6烷基等的基团所取代；R1、R2和R3各自独立地代表氢原子、氟基或C1到C6烷基；R4代表氢原子或前药基团；Y代表—CH2—CHR5—CH2—NHR6（其中R5代表氢原子、C1到C6烷基或C1到C6烷氧基，R6代表氢原子或前药基团）等，具有极好的TAFIa抑制活性，是治疗心肌梗死、心绞痛、急性冠状动脉综合征、脑梗死、深静脉血栓形成、肺栓塞等疾病的治疗药物。
• [EN] INDOLINE-CONTAINING SPIRO DERIVATIVE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN MEDICINE<br/>[FR] DÉRIVÉ SPIRO CONTENANT DE L'INDOLINE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION EN MÉDECINE<br/>[ZH] 含吲哚啉螺环类衍生物、其制备方法及其在医药上的应用
  申请人：[en]CHANGCHUN GENESCIENCE PHARMACEUTICAL CO., LTD.;[zh]长春金赛药业有限责任公司

  公开号：WO2022228318A1

  公开（公告）日：2022-11-03

  公开了一种式I所示的化合物及其消旋体、立体异构体、互变异构体、同位素标记物、氮氧化物、溶剂化物、多晶型物、代谢产物、酯、前药或其药学上可接受的盐，以及包含其的药物组合物，其制备方法，及其作为GHSR激动剂在制备诊断、预防和/或治疗生长激素依赖性疾病的药物中的用途，所述式I结构如下。