5(R)-methyl-4(R)hydroxypyrrolidinone | 461648-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 5(R)-methyl-4(R)hydroxypyrrolidinone
• 英文别名: (4R,5R)-4-hydroxy-5-methylpyrrolidin-2-one
• CAS: 461648-78-2
• 化学式: C₅H₉NO₂
• 分子量: 115.132
• InChiKey: ZBCVDJNHLQMBTG-QWWZWVQMSA-N

物化性质

• 沸点：
  330.3±35.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5(R)-methyl-4(R)hydroxypyrrolidinone 在 1,1'-双(二苯基膦)二茂铁 、 正丁基锂 、 sodium bis(2-methoxyethoxy)aluminum dihydride 、 水 、 palladium diacetate 、 三氧化硫吡啶 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 39.5h， 生成 5-[(2R, 3S)-1-(3-chloro-4-cyanophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]pyridine-2-carboxylic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists

  摘要：

  We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R-2) of the pyrrolidine ring increased the AR binding affinity. The (2S, 3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R-1) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.001
• 作为产物：
  描述：

  ethyl 1-[(S)-1-phenylethyl]aziridine-(R)-carboxylate 在 palladium dihydroxide sodium tetrahydroborate 、 氢气 、 氯化铵 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， -78.0~20.0 ℃ 、413.68 kPa 条件下， 反应 14.5h， 生成 5(R)-methyl-4(R)hydroxypyrrolidinone
  参考文献：
  名称：

  Syntheses of 1.BETA.-Methylcarbapenems Bearing 5-Methyl-4-hydroxypyrrolidinone.

  摘要：

  一系列带有5-甲基-4-巯基吡咯烷酮环的1β-甲基碳青霉烯类化合物1a—d已经被合成并评估了其体外抗菌活性和药代动力学参数。大多数化合物表现出了卓越的抗菌活性和对去氢肽酶-1的高稳定性。我们已经从手性纯的氮杂环丙烷酯合成了光学活性的5-甲基-4-羟基吡咯烷酮。

  DOI：

  10.1248/cpb.50.415

文献信息

• [EN] HETEROCYCLIC WDR5 INHIBITORS AS ANTI-CANCER COMPOUNDS<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE WDR5 UTILISÉS EN TANT QUE COMPOSÉS ANTICANCÉREUX
  申请人：NOVARTIS AG

  公开号：WO2021028806A1

  公开（公告）日：2021-02-18

  The present invention provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof; (I) which are inhibitors of WDR5. The present invention also provides pharmaceutical compositions comprising such compounds, compositions comprising such compounds with an additional therapeutic agent and the therapeutic uses of such compounds.

  本发明提供了式（I）的化合物或其药学上可接受的盐；（I）这些化合物是WDR5的抑制剂。本发明还提供了包含这些化合物的药物组合物，包含这些化合物与额外治疗剂的组合物以及这些化合物的治疗用途。
• FUSED BENZENE DERIVATIVE AND USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1553074B1

  公开（公告）日：2014-06-18
• Syntheses of 1.BETA.-Methylcarbapenems Bearing 5-Methyl-4-hydroxypyrrolidinone.
  作者：Do Kyu Pyun、Bong Jin Kim、Hee Jung Jung、Jae Hak Kim、Jin Soo Lee、Won Koo Lee、Cheol Hae Lee

  DOI：10.1248/cpb.50.415

  日期：——

  A new series of 1β-methylcarbapenems 1a—d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters. Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1. We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.

  一系列带有5-甲基-4-巯基吡咯烷酮环的1β-甲基碳青霉烯类化合物1a—d已经被合成并评估了其体外抗菌活性和药代动力学参数。大多数化合物表现出了卓越的抗菌活性和对去氢肽酶-1的高稳定性。我们已经从手性纯的氮杂环丙烷酯合成了光学活性的5-甲基-4-羟基吡咯烷酮。
• Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists
  作者：Satoshi Yamamoto、Hiromi Kobayashi、Tomohiro Kaku、Katsuji Aikawa、Takahito Hara、Masuo Yamaoka、Naoyuki Kanzaki、Atsushi Hasuoka、Atsuo Baba、Mitsuhiro Ito

  DOI：10.1016/j.bmc.2012.11.001

  日期：2013.1

  We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R-2) of the pyrrolidine ring increased the AR binding affinity. The (2S, 3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R-1) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide. (C) 2012 Elsevier Ltd. All rights reserved.