tert-butyl 3-((cyclopropylamino)methyl)azetidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: tert-butyl 3-((cyclopropylamino)methyl)azetidine-1-carboxylate
• 英文别名: Tert-butyl 3-((cyclopropylamino)methyl)azetidine-1-carboxylate；tert-butyl 3-[(cyclopropylamino)methyl]azetidine-1-carboxylate
• 化学式: C₁₂H₂₂N₂O₂
• 分子量: 226.319
• InChiKey: KASYKNWLVMRDCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-((cyclopropylamino)methyl)azetidine-1-carboxylate 在 盐酸 、 三乙胺 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 9.0h， 生成 4-[3-(3-[(cyclopropylamino)methyl]azetidine-1-carbonyl)-4-fluorobenzyl]phthalazin-1(2H)-one
  参考文献：
  名称：

  PROCESS FOR PREPARING A PHTHALAZINONE DERIVATIVE AND INTERMEDIATES THEREOF

  摘要：

  本申请提供了一种制备4-[3-(3-[(环丙基氨基)甲基]氮杂环己-1-甲酰基)-4-氟苯甲基]邻菲啰嗪-1(2H)-酮或其药学上可接受的盐的方法，以及制备中间体的方法、制备中间体的组合物和制备高纯度和收率的方法所得的包含该化合物的组合物和产品。

  公开号：

  US20210323946A1
• 作为产物：
  描述：

  3-甲酰基氮杂环丁烷-1-羧酸叔丁酯 在 sodium tetrahydroborate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 8.0h， 生成 tert-butyl 3-((cyclopropylamino)methyl)azetidine-1-carboxylate
  参考文献：
  名称：

  Exploration of 3-Aminoazetidines as Triple Reuptake Inhibitors by Bioisosteric Modification of 3-α-Oxyazetidine

  摘要：

  For a development of broad spectrum antidepressant 3-aminoazetidine derivatives, two series of compounds were explored by bioisosteric modification of 3-α-oxyazetidine. We synthesized 166 novel 3-aminoazetidine derivatives in series A and B, starting from Boc-protected 3-azetidinone (3) and Boc-protected 3-azetidinal (9) respectively, through parallel syntheses. The inhibitory reuptake activities against serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmitters were measured by the Neurotransmitter Transporter Uptake Assay Kit using the human embryonic kidney 293 (HEK293) cells stably transfected with the respective three kinds of human transporters (hSERT, hNET, and hDAT). Our study aimed to identify compounds having relative inhibitory activities against hSERT > hNET > hDAT. Lead optimization including microsomal stability, CYP, hERG assay, Ames test, BBB, and PK study resulted in the identification of compound 10dl as a candidate for further studies.

  DOI：

  10.1021/ml500187a

文献信息

• [EN] HTT MODULATORS FOR TREATING HUNTINGTON'S DISEASE<br/>[FR] MODULATEURS HTT POUR LE TRAITEMENT DE LA MALADIE DE HUNTINGTON
  申请人：CHDI FOUNDATION INC

  公开号：WO2021231571A1

  公开（公告）日：2021-11-18

  Provided herein are certain compounds useful as HTT modulators. Such compound are useful in the treatment of Huntington's disease.

  以下提供了一些作为HTT调节剂有用的化合物。这些化合物在亨廷顿病的治疗中很有用。
• CRYSTALLINE FORMS OF PHTHALAZINONE COMPOUND
  申请人：IDIENCE CO., LTD.

  公开号：US20210323945A1

  公开（公告）日：2021-10-21

  The present specification provides crystalline forms of 4-[3-(3-[(cyclopropylamino)methyl]azetidine-1-carbonyl)-4-fluorobenzyl]phthalazin-1 (2H)-one hydrochloride, methods of preparing the same, and pharmaceutical compositions comprising the same.

  本规范提供了4-[3-(3-[(环丙胺基)甲基]氮杂环丙烷-1-甲酰)-4-氟苯基]邻苯二嗪-1(2H)-酮盐酸晶型形式，制备该晶型形式的方法，以及包含该晶型形式的药物组合物。
• [EN] ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE-1 (ENPP1) INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'ECTONUCLÉOTIDE PYROPHOSPHATASE-PHOSPHODIESTÉRASE 1 (ENPP1) ET LEURS UTILISATIONS
  申请人：INTEGRAL BIOSCIENCES PRIVATE LTD

  公开号：WO2022091048A1

  公开（公告）日：2022-05-05

  The present invention discloses compounds useful in treatment of conditions associated with dysfunction of ectonucleotide pyrophosphatase / phosphodiesterase-1 (ENPP1) enzyme. Specifically, the present invention discloses compound of formula (J) which exhibit inhibitory activity against ENPP1. Method of treating conditions associated with over-expression of ENPP1 gene with such compound is disclosed. Uses thereof, pharmaceutical composition, and kits are also disclosed.

  本发明揭示了在治疗与外核苷酸焦磷酸酶/磷酸二酯酶-1 (ENPP1)酶功能障碍相关的疾病中有用的化合物。具体而言，本发明揭示了公式（J）的化合物，这些化合物表现出对ENPP1的抑制活性。揭示了使用这种化合物治疗与ENPP1基因过度表达相关的疾病的方法。还揭示了其用途、制药组合物和试剂盒。
• Crystalline forms of phthalazinone compound
  申请人：IDIENCE CO., LTD.

  公开号：US11390608B2

  公开（公告）日：2022-07-19

  The present specification provides crystalline forms of 4-[3-(3-[(cyclopropylamino)methyl]azetidine-1-carbonyl)-4-fluorobenzyl]phthalazin-1(2H)-one hydrochloride, methods of preparing the same, and pharmaceutical compositions comprising the same.

  本说明书提供了 4-[3-(3-[(环丙基氨基)甲基]氮杂环丁烷-1-甲酰基)-4-氟苄基]酞嗪-1(2H)-酮盐酸盐的结晶形式、其制备方法以及包含其的药物组合物。
• Identification and Optimization of RNA-Splicing Modulators as Huntingtin Protein-Lowering Agents for the Treatment of Huntington’s Disease
  作者：Longbin Liu、Karine Malagu、Alan F. Haughan、Vinod Khetarpal、Andrew J. Stott、William Esmieu、Huw D. Vater、Stephen J. Webster、Amanda J. Van de Poël、Cole Clissold、Brett Cosgrove、Benjamin Sutton、Jonathan A. Spencer、Perla Breccia、Emanuela Gancia、Silvia Bonomo、Tammy Ladduwahetty、Ovadia Lazari、Hiral Patel、Helen C. Atton、Steve Clifton、Daniel M. Mota、Dario Magnani、Amy O’Neill、Marta Stebbeds、Natsuko Macabuag、Daniel Todd、Maria E. Herva、Philip Mitchell、Mijke Visser、Sara Compte Sancerni、Laure Grand Moursel、Marta da Silva、Eva Kritikou、Taneli T. Heikkinen、Tamuna Bolkvadze、Valentina Fodale、Debora Spadafora、Manuel Daldin、Alberto Bresciani、John E. Mangette、Elizabeth M. Doherty、Matthew R. Lee、Todd Herbst、Edith Monteagudo、Douglas Macdonald、Nikolay V. Plotnikov、Mark Chambers、George McAllister、Ignacio Muňoz-Sanjuan、Celia Dominguez

  DOI：10.1021/acs.jmedchem.3c01173

  日期：2023.9.28