吗啉-2-甲腈 | 135782-24-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 吗啉-2-甲腈
• 中文别名: 2-氰基吗啉;；2-腈基吗啉；2-氰基吗啉
• 英文名称: 2-Cyanomorpholine
• 英文别名: morpholine-2-carbonitrile；cyanomorpholine
• CAS: 135782-24-0
• 化学式: C₅H₈N₂O
• mdl: MFCD01321090
• 分子量: 112.131
• InChiKey: HAASCECTXNYFCI-UHFFFAOYSA-N

物化性质

• 沸点：
  256.0±35.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少量）、二氯甲烷（少量）、甲醇（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 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：
  45
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  吗啉-2-甲腈 在 sodium azide 、 三丁基氯化锡 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (2-Isopropylphenyl)[2-nitro-4-(E-((3-(tetrazol-5-yl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide
  参考文献：
  名称：

  Discovery of Potent Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 3. Amide (C-Ring) Structure−Activity Relationship and Improvement of Overall Properties of Arylthio Cinnamides

  摘要：

  The interaction of LFA-1 and ICAM-1 plays an important role in the cell adhesion process. On the basis of previously reported SAR and structural information on the binding of our p-arylthiocinnamide series to LFA-1, we have identified the cyclic amide (C-ring) as a site for modification. Improvement in potency and, more importantly, in the physical properties and pharmacokinetic profiles of the leading compounds resulted from this modification. One of the best compounds (11f) is also shown to reduce myocardial infarct size in rat.

  DOI：

  10.1021/jm010059w
• 作为产物：
  描述：

  C.I.酸性橙108 、 2-氯丙烯腈 在 potassium tert-butylate 作用下， 生成 吗啉-2-甲腈
  参考文献：
  名称：

  The synthesis of 2-morpholine carboxylic acid derivatives and their elaboration to 1-aza-4-oxabicyclo[3.3.1]nonan-6-one.

  摘要：

  Two syntheses of novel 2-morpholine carboxylic acid derivatives are described. The esters were converted into 1-aza-4-oxabicyclo[3.3.1]nonan-6-one, the first example of this ring system, which was further elaborated to the ortho-methoxy benzamide derivative (2).

  DOI：

  10.1016/s0040-4039(00)79702-4

文献信息

• Discovery and Preclinical Profiling of 3-[4-(Morpholin-4-yl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant, and in Vivo Active LRRK2 Kinase Inhibitor
  作者：Jaclyn L. Henderson、Bethany L. Kormos、Matthew M. Hayward、Karen J. Coffman、Jayasankar Jasti、Ravi G. Kurumbail、Travis T. Wager、Patrick R. Verhoest、G. Stephen Noell、Yi Chen、Elie Needle、Zdenek Berger、Stefanus J. Steyn、Christopher Houle、Warren D. Hirst、Paul Galatsis

  DOI：10.1021/jm5014055

  日期：2015.1.8

  As such, LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the discovery and optimization of a novel series of potent LRRK2 inhibitors, focusing on improving kinome selectivity using a surrogate crystallography approach. This resulted in the identification of 14 (PF-06447475), a highly potent, brain penetrant and selective LRRK2 inhibitor which has been further

  富含亮氨酸的重复激酶2（LRRK2）已通过全基因组关联研究（GWAS）与帕金森氏病（PD）遗传相关。最常见的LRRK2突变G2019S在总人群中相对较少，导致激酶活性增加。这样，LRRK2激酶抑制剂可潜在地用于治疗PD。我们在此公开了一系列新颖的有效LRRK2抑制剂的发现和优化，其重点在于使用替代晶体学方法改善kinome的选择性。这导致鉴定出14（PF-06447475），这是一种高效的，脑渗透性和选择性LRRK2抑制剂，已在体内安全性和药效学研究中进行了进一步概述。
• EP1201661
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PYRIDINE DERIVATIVES WITH N-LINKED CYCLIC SUBSTITUENTS AS CGAS INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDINE AYANT DES SUBSTITUANTS CYCLIQUES À LIAISON N EN TANT QU'INHIBITEURS DE CGAS
  申请人：[en]BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：WO2022238327A1

  公开（公告）日：2022-11-17

  The invention relates to new proline derivatives of formula (I) as cGAS inhibitors, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11and G are defined as in claim 1, and prodrugs or pharmaceutically acceptable salts of these compounds for the treatment of diseases such as systemic lupus erythematosus, systemic sclerosis (SSc), non-alcoholic steatotic hepatitis (NASH), interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF).
• The synthesis of 2-morpholine carboxylic acid derivatives and their elaboration to 1-aza-4-oxabicyclo[3.3.1]nonan-6-one.
  作者：Frank D. King、Roger T. Martin

  DOI：10.1016/s0040-4039(00)79702-4

  日期：1991.5

  Two syntheses of novel 2-morpholine carboxylic acid derivatives are described. The esters were converted into 1-aza-4-oxabicyclo[3.3.1]nonan-6-one, the first example of this ring system, which was further elaborated to the ortho-methoxy benzamide derivative (2).
• Discovery of Potent Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 3. Amide (C-Ring) Structure−Activity Relationship and Improvement of Overall Properties of Arylthio Cinnamides
  作者：Zhonghua Pei、Zhili Xin、Gang Liu、Yihong Li、Edward B. Reilly、Nathan L. Lubbers、Jeffery R. Huth、James T. Link、Thomas W. von Geldern、Bryan F. Cox、Sandra Leitza、Yi Gao、Kennan C. Marsh、Peter DeVries、Greg F. Okasinski

  DOI：10.1021/jm010059w

  日期：2001.8.1

  The interaction of LFA-1 and ICAM-1 plays an important role in the cell adhesion process. On the basis of previously reported SAR and structural information on the binding of our p-arylthiocinnamide series to LFA-1, we have identified the cyclic amide (C-ring) as a site for modification. Improvement in potency and, more importantly, in the physical properties and pharmacokinetic profiles of the leading compounds resulted from this modification. One of the best compounds (11f) is also shown to reduce myocardial infarct size in rat.