N-(1,3-dihydroxy-2-methylpropan-2-yl)-2,2,2-trifluoroacetamide | 218162-46-0

• 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-(1,3-dihydroxy-2-methylpropan-2-yl)-2,2,2-trifluoroacetamide
• 英文别名: 2-methyl-2-trifluoroacetamido-1,3-propane-diol；2-methyl-2-trifluoroacetamido-1,3-propanediol
• CAS: 218162-46-0
• 化学式: C₆H₁₀F₃NO₃
• mdl: MFCD00465537
• 分子量: 201.146
• InChiKey: UTNMIALQEHSUDU-UHFFFAOYSA-N

物化性质

• 熔点：
  112-114 °C
• 沸点：
  349.4±42.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  原甲酸三乙酯 、 N-(1,3-dihydroxy-2-methylpropan-2-yl)-2,2,2-trifluoroacetamide 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 2,2,2-trifluoro-N-(2-methoxy-5-methyl-1,3-dioxan-5-yl)acetamide
  参考文献：
  名称：

  Tuning the pH sensitivities of orthoester based compounds for drug delivery applications by simple chemical modification

  摘要：

  Orthoesters are acid-sensitive moieties that allow substantial structural diversity for biological applications including drug delivery. Here, the pH-sensitivity of a range of novel orthoester based compounds was compared in the range 7.5-4.5 that is characteristic of the increased acidification during endocytosis. We find that simple modifications close to the orthoester had major effects on both the rate and extent of hydrolysis, suggesting this could be exploited for activating drug delivery systems on endocytic pathways. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.035
• 作为产物：
  描述：

  2-氨基-2-甲基-1,3-丙二醇 在 potassium carbonate 、 三氟乙酸酐 作用下， 以 N-甲基乙酰胺 为溶剂， 生成 N-(1,3-dihydroxy-2-methylpropan-2-yl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  Imidazolyl-cyclic acetals

  摘要：

  式（I）的化合物描述如下：其中R1是可选择取代的杂环芳基；R2是可选择取代的芳基或可选择取代的杂环芳基；R3是一个基团—L1—R7或—L2—R8【其中L1是可选择取代的烷基链；R7是氢、芳基、氰基、环烷基、杂环芳基、杂环烷基、硝基、—S(O)nR9、—NHSO2R9、—C(═Z)OR10、—C(═Z)R10、—OR10、—N(R11)—C(═Z)R9、—NY1Y2、—SO2NY1Y2、—C(═Z)—NY1Y2、—N(R11)—C(═Z)—NY1Y2、—N(OR10)—C(═Z)—NY1Y2、—N(OR10)—C(═Z)R10、—C(═NOR10)R10、—C(═Z)NR10OR12、—N(R11)—C(═NR13)—NY1Y2或—N(R11)—C(═Z)OR11；L2是直接键或由2到约6个碳原子组成的直链或支链碳链，含有双键或三键碳-碳键；R8是氢、芳基、环烯基、环烷基、杂环芳基或杂环烷基】；R4是一个基团—L3—R14【其中L3是直接键或可选择取代的烷基链，R14是氢、烷基、叠氮基、羟基、烷氧基、芳基、芳基烷氧基、芳氧基、羧基（或酸生物等构异体）、环烷氧基、杂环芳基、杂环芳基烷氧基、杂环芳氧基、杂环烷基、杂环烷氧基、硝基、—NY4Y5、—N(R10)—C(═Z)—R15；—N(R10)—C(═Z)—L4—R16、—NH—C(═Z)—NH—R15、—NH—C(═Z)—NH—L4—R16、—N(R10)—SO2—R15、—N(R10)—SO2—L4—R16、—S(O)nR9、—C(═Z)—NY4Y5或—C(═Z)—OR9】；R5是氢、烷基或羟基烷基；或者R4和R5，当连接到同一碳原子时，可以与所述碳原子形成环烷基、环烯基或杂环烷基环或基团C═CH2；R6是氢或烷基；m为零或整数1或2；以及其N-氧化物，以及它们的前药；以及式（I）的化合物及其N-氧化物的药学上可接受的盐和溶剂（例如水合物），以及它们的前药。这些化合物是肿瘤坏死因子抑制剂，可用作药物。

  公开号：

  US06602877B1

文献信息

• HYBRID ANTICANCER PRODRUG SIMULTANEOUSLY PRODUCING CINNAMALDEHYDE AND QUINONE METHIDE AND METHOD FOR PREPARING SAME
  申请人：INDUSTRIAL COOPERATION FOUNDATION CHONBUK NATIONAL UNIVERSITY

  公开号：US20170014518A1

  公开（公告）日：2017-01-19

  The present invention relates to a hybrid anticancer prodrug simultaneously producing cinnamaldehyde and quinone methide. The hybrid anticancer prodrug according to the present invention sequentially releases quinone methide and cinnamaldehyde by H 2 O 2 and acidic pH, and thus alkylates antioxidant GSH through the release of quinone methide, thereby inhibiting an antioxidative system and increasing oxidation stress, and generates and accumulates reactive oxygen species (ROS) through the release of cinnamaldehyde, thereby promoting apoptosis, and thus the hybrid anticancer prodrug according to the present invention can be favorably used as an anticancer drug by creating a synergetic anticancer effect through double stimulus-response and sequential treatment action in a cancer cell-specific manner.

  本发明涉及一种同时产生肉桂醛和醌甲醚的杂合抗癌前药。根据本发明的杂合抗癌前药通过过氧化氢和酸性pH依次释放醌甲醚和肉桂醛，从而通过释放醌甲醚来烷基化抗氧化剂GSH，抑制抗氧化系统并增加氧化应激，并通过释放肉桂醛产生和积累活性氧种（ROS），从而促进凋亡，因此，根据本发明的杂合抗癌前药可以通过在癌细胞特异性方式下的双重刺激-响应和顺序治疗作用产生协同抗癌效果，从而可以作为抗癌药物有利地使用。
• The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy
  作者：Iain M. McLay、Frank Halley、John E. Souness、Jeffrey McKenna、Veronique Benning、Mark Birrell、Brenda Burton、Maria Belvisi、Alan Collis、Alex Constan、Martyn Foster、David Hele、Zaid Jayyosi、Mike Kelley、Chris Maslen、Glen Miller、Marie-Claude Ouldelhkim、Kenneth Page、Simon Phipps、Kenneth Pollock、Barry Porter、Andrew J. Ratcliffe、Elisabeth J. Redford、Stephen Webber、Bryan Slater、Veronique Thybaud、Nicola Wilsher

  DOI：10.1016/s0968-0896(00)00331-x

  日期：2001.2

  RPR132331, a 2-(2-dioxanyl)imidazole. was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNF alpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Chirality-directed organogel formation
  作者：Remir G. Kostyanovsky、Denis A. Lenev、Oleg N. Krutius、Andrey A. Stankevich

  DOI：10.1070/mc2005v015n04abeh002136

  日期：2005.1

  New low molecular mass enantiopure organogelators (1R,4R)-1, (S)-2, (R)-3 and (R)-4 were found; racemates (R,S)-3 and (R,S)-4 have only a moderate gelating power, whereas (R,S)-1 and (R,S)-2 do not show gelating properties at all.
• IMIDAZOLYL-CYCLIC ACETALS
  申请人：RHONE-POULENC RORER LIMITED

  公开号：EP0988301A1

  公开（公告）日：2000-03-29
• US6602877B1
  申请人：——

  公开号：US6602877B1

  公开（公告）日：2003-08-05