(S)-[(3aR,4R,6R,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-(4-chlorophenyl)methanol | 1385036-05-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-[(3aR,4R,6R,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-(4-chlorophenyl)methanol
• CAS: 1385036-05-4
• 化学式: C₁₅H₁₉ClO₅
• 分子量: 314.766
• InChiKey: MVQBKKNTQPPEBF-RYMFRWLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-[(3aR,4R,6R,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-(4-chlorophenyl)methanol 在 水 、 三苯基膦 、 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 74.5h， 生成 (1R)-(4-chlorophenyl)((2S,3S,4R)-3,4,5-trihydroxytetrahydrofuran-2-yl)methyl [1,1'-biphenyl]-4-carboxylate
  参考文献：
  名称：

  [EN] SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5)
  [FR] INHIBITEURS SÉLECTIFS DE LA PROTÉINE ARGININE MÉTHYLTRANSFÉRASE 5 (PRMT5)

  摘要：

  该披露涉及到Formula I、Formula II、Formula III和Formula IV的化合物：(I) (II) (III) (IV) 同时还描述了它们的使用和制备方法。

  公开号：

  WO2018160855A1
• 作为产物：
  描述：

  (3aR,4S,6R,6aR)-tetrahydro-6-methoxy-2,2-dimethylfuro-[3,4-d][1,3]dioxole-4-carbaldehyde 、 4-氯苯硼酸 在 diethylzinc 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以77%的产率得到(S)-[(3aR,4R,6R,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-(4-chlorophenyl)methanol
  参考文献：
  名称：

  Diastereoselective Addition of Arylzinc Reagents to Sugar Aldehydes

  摘要：

  The diastereoselective arylation of sugar-derived aldehydes is described. The arylating reagents are generated in situ by a boron-to-zinc exchange reaction of arylboronic acids with Et2Zn to generate arylethylzinc reagents. The exquisite reactivity of the arylzinc reagents allowed for an efficient and mild arylation, delivering the corresponding products in diastereolsomeric ratios of up to >20:1. The utility of the methodology is highlighted with an efficient formal synthesis of (+)-7-epl-goniofufurone, a member of the styryllactone family of natural products.

  DOI：

  10.1021/ol301724x

文献信息

• Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors
  作者：Hong Lin、Min Wang、Yang W. Zhang、Shuilong Tong、Raul A. Leal、Rupa Shetty、Kris Vaddi、Juan I. Luengo

  DOI：10.1021/acsmedchemlett.9b00074

  日期：2019.7.11

  Protein arginine methyltransferase 5 (PRMT5) is known to symmetrically dimethylate numerous cytosolic and nuclear proteins that are involved in a variety of cellular processes. Recent findings have revealed its potential as a cancer therapeutic target. PRMT5 possesses a cysteine (C449) in the active site, unique to PRMT5. Therefore, covalent PRMT5 inhibition is an attractive chemical approach. Herein

  已知蛋白精氨酸甲基转移酶5（PRMT5）对称地二甲基化许多参与多种细胞过程的胞质和核蛋白。最近的发现揭示了其作为癌症治疗靶标的潜力。PRMT5在活动部位具有PRMT5独有的半胱氨酸（C449）。因此，共价PRMT5抑制是一种有吸引力的化学方法。在本文中，我们报告了一系列令人兴奋的发现，它们在生理条件下可以转化为醛类并与C449反应形成共价加合物，据推测，该共价加合物经历了前所未有的消除，从而形成了硫醇-乙烯基醚，如电子密度所示。在PRMT5 / MEP50复合物的共晶体结构中。
• [EN] SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5<br/>[FR] INHIBITEURS SÉLECTIFS DE LA PROTÉINE ARGININE MÉTHYLTRANSFÉRASE 5
  申请人：PRELUDE THERAPEUTICS INC

  公开号：WO2020206308A1

  公开（公告）日：2020-10-08

  The disclosure is directed to methods of treating disease using compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI:

  披露的内容涉及使用以下化合物治疗疾病的方法：Formula I、Formula II、Formula III、Formula IV、Formula V或Formula VI。
• Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
  申请人：PRELUDE THERAPEUTICS, INCORPORATED

  公开号：US11220524B2

  公开（公告）日：2022-01-11

  The disclosure is directed to compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI: Methods of their use in inhibiting a protein arginine methyltransferase 5 (PRMT5) enzyme and treating disease, as well as methods of their preparation are also described.

  本公开涉及式 I、式 II、式 III、式 IV、式 V 或式 VI 的化合物：还描述了它们在抑制蛋白精氨酸甲基转移酶 5 (PRMT5) 酶和治疗疾病中的使用方法，以及它们的制备方法。
• SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5)
  申请人：PRELUDE THERAPEUTICS, INCORPORATED

  公开号：US20210130388A1

  公开（公告）日：2021-05-06

  The disclosure is directed to compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI: Methods of their use in inhibiting a protein arginine methyltransferase 5 (PRMT5) enzyme and treating disease, as well as methods of their preparation are also described.
• Selective Inhibitors Of Protein Arginine Methyltransferase 5 (PRMT5)
  申请人：Prelude Therapeutics, Incorporated

  公开号：US20220218732A1

  公开（公告）日：2022-07-14

  The disclosure is directed to methods of treating disease using compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI: