顺式3,4-二羟基吡咯烷盐酸盐 | 186393-21-5

• 物质功能分类: 有机原料 - 氨基化合物 - 环烷胺、芳香单胺、芳香多胺及其衍生物和盐
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 顺式3,4-二羟基吡咯烷盐酸盐
• 英文名称: cis-pyrrolidine-3,4-diol hydrochloride
• 英文别名: (3R,4S)-pyrrolidine-3,4-diol hydrochloride；(3R,4S)-3,4-Dihydroxypyrrolidine hydrochloride；(3R,4S)-pyrrolidine-3,4-diol;hydrochloride
• CAS: 186393-21-5
• 化学式: C₄H₉NO₂*ClH
• mdl: MFCD21602660
• 分子量: 139.582
• InChiKey: VADWFRGDDJHKNB-HKTIBRIUSA-N

物化性质

• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.63
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  52.5
• 氢给体数：
  4
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  顺式3,4-二羟基吡咯烷盐酸盐 、 N-[(1R)-1-(4-bromophenyl)ethyl]-1-methyl-3-phenyl-1H-pyrazole-5-carboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以23%的产率得到N-[(1R)-1-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}ethyl]-1-methyl-3-phenyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis

  摘要：

  Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of BI-4916, a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD(+))-competitive PHGDH inhibitor BI-4924, which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening, a subsequent hit optimization using structure-based drug design was conducted to deliver a single-digit nanomolar lead series and to improve potency by 6 orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD(+).

  DOI：

  10.1021/acs.jmedchem.9b00718
• 作为产物：
  描述：

  tert-butyl (3R,4S)-3,4-dihydroxypyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以97%的产率得到顺式3,4-二羟基吡咯烷盐酸盐
  参考文献：
  名称：

  [EN] THIENO-PYRIDINE DERIVATIVES AS MEK INHIBITORS
  [FR] DÉRIVÉS DE THIÉNO-PYRIDINE UTILISÉS COMME INHIBITEURS DE MEK

  摘要：

  一系列噻吩[2,3-6]吡啶衍生物，连接在取代苯胺基团的2-位置，其在3-位置被一个与吡咯啉-1-基环相连的羰基取代，后者又构成一个含杂原子的融合双环环系统的一部分，是人类MEK（MAPKK）酶的选择性抑制剂，在医学上具有益处，例如在治疗炎症、自身免疫、心血管、增殖（包括肿瘤学）和疼痛性疾病方面。

  公开号：

  WO2009153554A1

文献信息

• [EN] SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1<br/>[FR] PYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE DNMT1
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017216726A1

  公开（公告）日：2017-12-21

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及取代吡啶衍生物。具体而言，该发明涉及符合以下式（Iar）的化合物：（Iar）其中Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar和R5ar如本文所定义；或其药学上可接受的盐或前药。该发明的化合物是DNMT1的选择性抑制剂，可用于治疗癌症、癌前综合征、β血红蛋白病、镰状细胞病、镰状细胞贫血、β地中海贫血以及与DNMT1抑制相关的疾病。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制DNMT1活性和治疗相关疾病的方法。
• Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors targeting Escherichia coli type I signal peptidase
  作者：Natalia Szałaj、Lu Lu、Andrea Benediktsdottir、Edouard Zamaratski、Sha Cao、Gustav Olanders、Charles Hedgecock、Anders Karlén、Máté Erdélyi、Diarmaid Hughes、Sherry L. Mowbray、Peter Brandt

  DOI：10.1016/j.ejmech.2018.08.086

  日期：2018.9

  Type I signal peptidase, with its vital role in bacterial viability, is a promising but underexploited antibacterial drug target. In the light of steadily increasing rates of antimicrobial resistance, we have developed novel macrocyclic lipopeptides, linking P2 and P1′ by a boronic ester warhead, capable of inhibiting Escherichia coli type I signal peptidase (EcLepB) and exhibiting good antibacterial

  I型信号肽酶在细菌生存能力中起着至关重要的作用，是一种有前途但未充分利用的抗菌药物靶标。鉴于抗菌药耐药率的稳定增长，我们开发了一种新型的大环脂肽，通过硼酸酯战斗部连接P2和P1'，能够抑制大肠杆菌I型信号肽酶（Ec LepB）并表现出良好的抗菌活性。大环环，肽序列和亲脂性尾巴的结构修饰使我们得到了14种新颖的大环硼酸酯。这可以表明，大环来讲是很好的耐受性的EcLepB抑制和抗菌活性。在合成的大环化合物中， 鉴定出低纳摩尔范围的有效酶抑制剂（例如化合物42f，Ec LepB IC 50 = 29 nM）也显示出良好的抗菌活性（例如化合物42b，大肠杆菌WT MIC = 16μg/ mL）。这里描述的独特的大环硼酸酯是基于以前发表的线性脂肽EcLepB抑制剂试图解决细胞毒性和溶血作用。我们在本文中显示，大环的结构变化会影响细胞毒性和溶血活性，这表明P2至P1'接头提供了优化脱靶效应的手段。然而
• IONIZABLE COMPOUNDS AND COMPOSITIONS AND USES THEREOF
  申请人：Nitto Denko Corporation

  公开号：US20160376229A1

  公开（公告）日：2016-12-29

  This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

  这项发明涉及可离子化的化合物，以及其组合物和使用方法。这些可离子化的化合物可用于制备纳米粒子组合物，用于生物制药和治疗。更具体地说，这项发明涉及提供纳米粒子以包裹活性剂，如核酸剂，并将活性剂传递和分发到细胞、组织、器官和受试者的化合物、组合物和方法。
• [EN] PYRAZOLOPYRIMIDINES HAVING ACTIVITY AGAINST THE RESPIRATORY SYNCYTIAL VIRUS (RSV)<br/>[FR] PYRAZOLOPYRIMIDINES AYANT UNE ACTIVITÉ CONTRE LE VIRUS RESPIRATOIRE SYNCYTIAL (VRS)
  申请人：JANSSEN SCIENCES IRELAND UNLIMITED CO

  公开号：WO2019106004A1

  公开（公告）日：2019-06-06

  The invention concerns compounds having antiviral activity, in particular, having an inhibitory activity on the replication of the respiratory syncytial virus (RSV). The invention further concerns pharmaceutical compositions comprising these compounds and the compounds for use in the treatment of respiratory syncytial virus infection. Formula (Ia).

  这项发明涉及具有抗病毒活性的化合物，特别是对呼吸道合胞病毒（RSV）复制具有抑制活性的化合物。该发明还涉及包含这些化合物的药物组合物，以及用于治疗呼吸道合胞病毒感染的化合物。公式（Ia）。
• 7-SUBSTITUTED 1-ARYL-NAPHTHYRIDINE-3-CARBOXYLIC ACID AMIDES AND USE THEREOF
  申请人：Bayer Aktiengesellschaft

  公开号：US20190263805A1

  公开（公告）日：2019-08-29

  The present application relates to novel 7-substituted 1-arylnaphthyridine-3-carboxamides, to processes for their preparation, to their use, alone or in combinations, for the treatment and/or prevention of diseases, and to their use for the production of medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular disorders and/or renal disorders.

  本申请涉及新颖的7-取代的1-芳基喹啉并吡啶-3-羧酰胺，其制备方法，其单独或组合使用，用于治疗和/或预防疾病，以及用于生产药物以治疗和/或预防疾病，特别是用于治疗和/或预防心血管疾病和/或肾脏疾病。