1-(乙氧基甲基)-6-(苯基甲基)-5-丙-2-基嘧啶-2,4-二酮 | 149950-60-7

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-(乙氧基甲基)-6-(苯基甲基)-5-丙-2-基嘧啶-2,4-二酮
• 中文别名: 6-苄基-1-(乙氧基甲基)-5-异丙基尿嘧啶
• 英文名称: Emivirine
• 英文别名: 1-(ethoxymethyl)-5-(1-methylethyl)-6-(phenylmethyl)pyrimidine-2,4(1H,3H)-dione；1-(ethoxymethyl)-6-(phenylmethyl)-5-propan-2-ylpyrimidine-2, 4-dione；6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione；6-benzyl-1-(ethoxymethyl)-5-isopropyluracil；6-benzyl-1-ethoxymethyl-5-isopropyluracil；MKC-442；6-benzyl-1-(ethoxymethyl)-5-propan-2-ylpyrimidine-2,4-dione
• CAS: 149950-60-7
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: MLILORUFDVLTSP-UHFFFAOYSA-N

物化性质

• 熔点：
  109.1-110.7 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 储存条件：
  存放在2-8℃环境下，应密封并保持干燥。

制备方法与用途

埃米维林(MKC-442)是一种非核苷逆转录酶抑制剂(NNRTI)，其依赖于DNA或RNA聚合酶对dTTP和dGTP的Ki值分别为0.20μM和0.01μM。研究表明，埃米维林表现出有效且选择性的抗人类免疫缺陷病毒1型(HIV-1)活性[1][2]。

反应信息

• 作为反应物：
  描述：

  1-(乙氧基甲基)-6-(苯基甲基)-5-丙-2-基嘧啶-2,4-二酮 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以72%的产率得到6-benzyl-1-(ethoxymethyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase

  摘要：

  A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of human immunodeficiency virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.

  DOI：

  10.1021/ml1002162
• 作为产物：
  描述：

  2-(4-bromo-2,6-dimethoxypyrimidin-5-yl)propan-2-ol 在 盐酸 、 三乙基硅烷 、 苯磺酰胺 、 lithium chloro-isopropyl-magnesium chloride 、 三氟甲磺酸三甲基硅酯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， -45.0~20.0 ℃ 、100.0 kPa 条件下， 反应 45.0h， 生成 1-(乙氧基甲基)-6-(苯基甲基)-5-丙-2-基嘧啶-2,4-二酮
  参考文献：
  名称：

  Chemo- and Regioselective Functionalization of Uracil Derivatives. Applications to the Synthesis of Oxypurinol and Emivirine

  摘要：

  A novel route for the synthesis of 4,5-difunctionalized uracils using a chemo-and regioselective bromine/magnesium exchange reaction on 5-bromo-4-halogeno-2,6-dimethoxypyrimidines has been developed. Applications to the synthesis of pharmaceuticals such as oxypurinol and emivirine are reported.

  DOI：

  10.1021/ol061295+

文献信息

• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。
• [EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2017046658A1

  公开（公告）日：2017-03-23

  Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.

  Amernita毒素的衍生物的化学式（I），其中，化学式（a）中的R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、X、L、m、n和Q在此处被定义。这些衍生物的制备。这些衍生物在靶向治疗癌症、自身免疫性疾病和传染病中的治疗用途。
• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190300521A1

  公开（公告）日：2019-10-03

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为SMARCA2或BRM（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合Von Hippel-Lindau E3泛素连接酶的配体，另一端结合靶蛋白的双功能化合物，使得靶蛋白与泛素连接酶靠近以实现靶蛋白的降解（和抑制）。本公开展示了与靶蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由靶蛋白聚集或积累导致的疾病或紊乱。