(1S,2S,4R)-4-氨基-2-(羟甲基)环戊烷-1-醇 | 1007126-28-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1S,2S,4R)-4-氨基-2-(羟甲基)环戊烷-1-醇
• 英文名称: (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol
• 英文别名: (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentan-1-ol
• CAS: 1007126-28-4
• 化学式: C₆H₁₃NO₂
• 分子量: 131.175
• InChiKey: XZINXOOZVCWXSP-JKUQZMGJSA-N

物化性质

• 沸点：
  266.7±25.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,2S,4R)-4-氨基-2-(羟甲基)环戊烷-1-醇 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 异丙醇 、 仲丁醇 为溶剂， 130.0 ℃ 、600.01 kPa 条件下， 生成 去磺酰胺基MLN4924
  参考文献：
  名称：

  Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat

  摘要：

  A practical synthesis of a novel NEDD8-activating enzyme (NAE) inhibitor pevonedistat (MLN4924) is described. Key steps include an enantioselective synthesis of an amino-diol cyclopentane intermediate containing three chiral centers and a novel, regioselective sulfamoylation using N-(tert-butoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide. The linear process, involving six solid isolations, has been carried out in multiple cGMP productions on 15-30 kg scale to produce pevonedistat in 98% (a/a) chemical purity and 25% overall yield.

  DOI：

  10.1021/acs.oprd.5b00209
• 作为产物：
  描述：

  ((1S,3S,5S)-3-(三苯甲基)-6-氧杂二环[3.1.0]己烷-1-基)甲醇 在 硼烷四氢呋喃络合物 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (1S,2S,4R)-4-氨基-2-(羟甲基)环戊烷-1-醇
  参考文献：
  名称：

  Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat

  摘要：

  A practical synthesis of a novel NEDD8-activating enzyme (NAE) inhibitor pevonedistat (MLN4924) is described. Key steps include an enantioselective synthesis of an amino-diol cyclopentane intermediate containing three chiral centers and a novel, regioselective sulfamoylation using N-(tert-butoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide. The linear process, involving six solid isolations, has been carried out in multiple cGMP productions on 15-30 kg scale to produce pevonedistat in 98% (a/a) chemical purity and 25% overall yield.

  DOI：

  10.1021/acs.oprd.5b00209

文献信息

• [EN] HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME<br/>[FR] COMPOSÉS HÉTÉROARYLE UTILES EN TANT QU'INHIBITEURS DE L'ENZYME D'ACTIVATION SUMO
  申请人：DUFFEY MATTHEW O

  公开号：WO2016004136A1

  公开（公告）日：2016-01-07

  Disclosed are chemical entities which are compounds of formula (I); or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra', Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

  公开了公式(I)的化合物或其药物可接受的盐； 其中Y、Ra、Ra'、Rb、Rc、X1、X2、X3、Rd、Z1和Z2具有本文所述的值，并且星号位置表示的立体化学配置指示绝对立体化学。 根据本公开的化学实体可用作Sumo激活酶（SAE）的抑制剂。 进一步提供了包含本公开化合物的药物组合物以及使用该组合物治疗增殖性、炎症性、心血管和神经退行性疾病或病症的方法。
• Development of Potent NEDD8-Activating Enzyme Inhibitors Bearing a Pyrimidotriazole Scaffold
  作者：Chaodong Xiong、Lina Zhou、Jing Tan、Shanshan Song、Xubin Bao、Ning Zhang、Huaqian Ding、Jiannan Zhao、Jin-xue He、Ze-Hong Miao、Ao Zhang

  DOI：10.1021/acs.jmedchem.1c00242

  日期：2021.5.13

  development of new inhibitors with both high potency and better safety profiles are urgently needed. Here, we report a structural hopping strategy by optimizing the central deazapurine framework and the solvent interaction region of compound 1, leading to compound 26 bearing a pyrimidotriazole scaffold. Compound 26 not only has compatible potency in the biochemical and cell assays but also possesses improved

  泛素样蛋白NEDD8是关键信号分子，与细胞的功能维持和体内平衡有关。该过程的失调涉及多种人类疾病，包括癌症。因此，NEDD8激活酶E1（NAE），是二烯化途径的唯一激活酶，已成为新兴的抗癌靶标。鉴于临床NAE抑制剂培维酮他汀（化合物1，MLN4924）的单药反应中等，迫切需要开发具有高效力和更好安全性的新型抑制剂。在这里，我们报告了一种结构跳变策略，该策略通过优化中心去氮杂嘌呤骨架和化合物1的溶剂相互作用区域来实现，从而形成化合物26带有嘧啶三唑支架。化合物26不仅具有在生物化学和细胞测定兼容效力而且具有改善的药物动力学（PK）比化合物性质1。在体内，化合物26在异种移植模型中显示出显着的抗肿瘤功效和良好的安全性。
• Process for the synthesis of E1 activating enzyme inhibitors
  申请人：Armitage Ian

  公开号：US20090036678A1

  公开（公告）日：2009-02-05

  The present invention provides processes and synthetic intermediates for the synthesis of 4-substituted ((1S,2S,4R)-2-hydroxy-4-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates, which are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.

  本发明提供了用于合成4-取代((1S,2S,4R)-2-羟基-4-7H-吡咯并[2,3-d]嘧啶-7-基}环戊基)甲基磺酸酯的过程和合成中间体，该化合物是E1激活酶抑制剂，可用于治疗细胞增殖紊乱，特别是癌症，以及与E1活性相关的其他紊乱。
• [EN] INDOLE-SUBSTITUTED PYRROLOPYRIMIDINYL INHIBITORS OF Uba6<br/>[FR] INHIBITEURS DE PYRROLOPYRIMIDINYLE SUBSTITUÉ PAR INDOLE D'UBA6
  申请人：MILLENNIUM PHARM INC

  公开号：WO2014022744A1

  公开（公告）日：2014-02-06

  Disclosed are chemical entities that inhibit Uba6, each of which is a compound of Formula /: Formula (I) or a pharmaceutically acceptable salt thereof, wherein R*1 is -H or -CH3; and Y is Formula (II) or Formula (III), wherein R2 is -H, -CH3 or C1-4 alkyloxycarbonyl; and RS7.1, RS7.2 and RS8.1 are defined herein; pharmaceutical compositions comprising the chemical entities; and methods of using the chemical entities. These chemical entities are useful for treating disorders, particularly cell proliferation disorders, including cancers.

  本文披露了抑制Uba6的化学实体，每个实体都是化合物Formula (I)或其药学上可接受的盐，其中R*1为-H或-CH3；Y为Formula (II)或Formula (III)，其中R2为-H，- 或C1-4烷氧羰基；RS7.1，RS7.2和RS8.1在此有定义；包括这些化学实体的药物组合物；以及使用这些化学实体的方法。这些化学实体对治疗疾病特别是细胞增殖紊乱，包括癌症，具有用处。
• TRIAZOLOPYRIMIDINE COMPOUND AND SALT, COMPOSITION AND USE THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP3985007A1

  公开（公告）日：2022-04-20

  The present disclosure relates to triazolopyrimidine compounds and salts, compositions and uses thereof, and the triazolopyrimidine compounds have the structures represented by the formula (I): the above-mentioned triazolopyrimidine compounds have good activity and high selectivity for NAE.

  本公开涉及三唑嘧啶化合物及其盐、组合物和用途，其中所述的三唑嘧啶化合物具有以下式（I）所表示的结构：上述三唑嘧啶化合物对NAE具有良好的活性和高选择性。