(2S,4S)-4-fluoro-2-(methoxymethyl)pyrrolidine | 877758-81-1

• 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: (2S,4S)-4-fluoro-2-(methoxymethyl)pyrrolidine
• CAS: 877758-81-1
• 化学式: C₆H₁₂FNO
• 分子量: 133.166
• InChiKey: WKFUQIUEAJAKPK-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,4S)-4-fluoro-2-(methoxymethyl)pyrrolidine 在 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.42h， 生成 (2S,4S)-N-butyl-5-[1-(4-fluoro-2-methoxymethylpyrrolidinyl)sulfonyl]isatin
  参考文献：
  名称：

  Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7

  摘要：

  A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as F-18-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the mu M scale, whereas all 4-OPEG(4) (PEG(4) = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.011
• 作为产物：
  描述：

  (2S,4S)-N-(tert-butyloxy)carbonyl-4-fluoro-2-methoxymethylpyrrolidine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2S,4S)-4-fluoro-2-(methoxymethyl)pyrrolidine
  参考文献：
  名称：

  Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7

  摘要：

  A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as F-18-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the mu M scale, whereas all 4-OPEG(4) (PEG(4) = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.011

文献信息

• VLA-4 INHIBITORY DRUG
  申请人：Machinaga Nobuo

  公开号：US20090233901A1

  公开（公告）日：2009-09-17

  There is provided a VLA-4 inhibitory drug having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally. A compound represented by the following formula (I): wherein R 1 represents a hydrogen atom or a C1-8 alkyl group; R 2 represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group, or a benzyloxy group which may be substituted; Q represents a monocyclic or bicyclic nitrogen-containing heterocyclic group which may be substituted, and has a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents a bicyclic aromatic hydrocarbon ring group which may be substituted, or a bicyclic aromatic heterocyclic group which may be substituted; R 3a , R 3b and R 3c each independently represent a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; and A 1 represents a nitrogen atom or C—R 3d (wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group), or a salt thereof, or a VLA-4 inhibitory drug comprising the compound or the salt as an active ingredient.

  提供了一种VLA-4抑制剂药物，具有良好的口服吸收性，并在口服给药时表现出足够的抗炎效果。其中，化合物的表示式如下（I）：其中，R1表示氢原子或C1-8烷基；R2表示氢原子、卤素原子、C1-8烷氧基或可取代的苄氧基；Q表示可取代的单环或双环含氮杂环基团，并具有氮原子作为键合位点；Y表示氧原子或CH2；W表示可取代的双环芳香烃环基团或可取代的双环芳香杂环基团；R3a、R3b和R3c分别独立地表示氢原子、卤素原子、C1-8烷氧基或C1-8烷基；A1表示氮原子或C-R3d（其中，R3d表示氢原子、卤素原子、C1-8烷氧基或C1-8烷基），或其盐，或包含该化合物或其盐作为活性成分的VLA-4抑制剂药物。
• VLA-4 inhibitory drug
  申请人：Machinaga Nobuo

  公开号：US20130065882A1

  公开（公告）日：2013-03-14

  This invention relates to a VLA-4 inhibitory drug, having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally, wherein an active ingredient is represented by formula (I), or a salt thereof: Q represents an optionally-substituted monocyclic or bicyclic nitrogen-containing heterocyclic group having a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents an optionally-substituted bicyclic aromatic hydrocarbon ring group or an optionally-substituted bicyclic aromatic heterocyclic group; A 1 represents a nitrogen atom or C—R 3d wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; R 1 represents H or a C1-8 alkyl group; R 2 represents H, a halogen, a C1-8 alkoxy

  本发明涉及一种VLA-4抑制剂药物，具有良好的口服吸收性，并在口服给药时展现足够的抗炎效果，其中活性成分由公式（I）或其盐表示： Q代表一个可选取代的含氮杂环基团，其为单环或双环结构，其中氮原子为键合位点； Y代表一个氧原子或CH2； W代表一个可选取代的双环芳香烃环基团或可选取代的双环芳香杂环基团； A1代表一个氮原子或C-R3d，其中R3d代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团； R1代表氢原子或C1-8烷基团； R2代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团。
• [EN] KRAS G12C INHIBITOR AND APPLICATION THEREOF<br/>[FR] INHIBITEUR DE KRAS G12C ET APPLICATION ASSOCIÉE<br/>[ZH] KRAS G12C抑制剂及其应用
  申请人：SHANGHAI DE NOVO PHARMATECH CO LTD

  公开号：WO2021063346A1

  公开（公告）日：2021-04-08

  一种新型的KRAS G12C抑制剂，如式（I）所示化合物、其异构体或药学上可接受的盐具有如下结构。如式（I）所示化合物及其组合物可以有效治疗与KRAS G12C相关的疾病，例如：癌症。
• US8129366B2
  申请人：——

  公开号：US8129366B2

  公开（公告）日：2012-03-06