(S)-1-amino-2,3-dihydro-1H-indene-5-carbonitrile | 903630-35-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (S)-1-amino-2,3-dihydro-1H-indene-5-carbonitrile
• 英文别名: (1S)-1-amino-2,3-dihydro-1H-indene-5-carbonitrile
• CAS: 903630-35-3
• 化学式: C₁₀H₁₀N₂
• 分子量: 158.203
• InChiKey: QNZWGKXBLSVMLQ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-1-amino-2,3-dihydro-1H-indene-5-carbonitrile 、 5-bromo-3-(furan-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 在 [(2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1, 1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate 、 对甲苯磺酸 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 24.0h， 生成 1-((3-(furan-3-yl)-1H-indazol-5-yl)amino)-2,3-dihydro-1H-indene-5-carbonitrile
  参考文献：
  名称：

  G2019S-LRRK2 激酶活性的脑渗透型氰茚烷和氰四氢萘抑制剂

  摘要：

  LRRK2 的 G2019S 变体会导致激酶活性增加，与帕金森病 (PD) 的发生有关。LRRK2 的强效、突变选择性和脑渗透抑制剂可以抑制 G2019S-LRRK2 特有的导致致病性的生物效应。我们报告了一系列氰茚烷和氰四氢萘激酶抑制剂的发现，最终形成化合物34，该化合物显示出对小鼠大脑中 LRRK2 磷酸化的选择性抑制。这些新型抑制剂可能进一步为未来帕金森病治疗开辟精准医疗之路。

  DOI：

  10.1016/j.bmcl.2023.129487
• 作为产物：
  描述：

  5-氰基-1-茚满酮 在 磷酸吡哆醛 、 Q25F/M60W/W64F/I266A mutant of ω-transaminase from Caulobacter sp. 、 异丙胺 作用下， 以 甲醇 为溶剂， 以63 %的产率得到(S)-1-amino-2,3-dihydro-1H-indene-5-carbonitrile
  参考文献：
  名称：

  Mechanism‐Guided Computational Design of ω‐Transaminase by Reprograming of High‐Energy‐Barrier Steps

  摘要：

  Abstractω‐Transaminases (ω‐TAs) show considerable potential for the synthesis of chiral amines. However, their low catalytic efficiency towards bulky substrates limits their application, and complicated catalytic mechanisms prevent precise enzyme design. Herein, we address this challenge using a mechanism‐guided computational enzyme design strategy by reprograming the transition and ground states in key reaction steps. The common features among the three high‐energy‐barrier steps responsible for the low catalytic efficiency were revealed using quantum mechanics (QM). Five key residues were simultaneously tailored to stabilize the rate‐limiting transition state with the aid of the Rosetta design. The 14 top‐ranked variants showed 16.9–143‐fold improved catalytic activity. The catalytic efficiency of the best variant, M9 (Q25F/M60W/W64F/I266A), was significantly increased, with a 1660‐fold increase in kcat/Km and a 1.5–26.8‐fold increase in turnover number (TON) towards various indanone derivatives.

  DOI：

  10.1002/anie.202212555

文献信息

• Metalloprotease inhibitors
  申请人：Sucholeiki Irving

  公开号：US20080021024A1

  公开（公告）日：2008-01-24

  The present invention relates to amide containing aromatic MMP inhibiting compounds with a mono-amide heteroaromatic group, of formulas I and II:

  本发明涉及具有含芳香族MMP抑制化合物的酰胺，其具有单酰胺杂芳基团，化学式I和II：
• Heterobicyclic metalloprotease inhibitors
  申请人：Gallagher M. Brian

  公开号：US20070155737A1

  公开（公告）日：2007-07-05

  The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic ADAMTS-4 inhibiting compounds.

  本发明通常涉及含有酰胺基团的药物，特别是含有酰胺基团的杂双环金属蛋白酶抑制剂化合物。更具体地，本发明提供了一类新的杂双环ADAMTS-4抑制剂化合物。
• DIPEPTIDYL PEPTIDASE-IV INHIBITORS
  申请人：Kroth Heiko

  公开号：US20100009961A1

  公开（公告）日：2010-01-14

  The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.
• Heterobicyclic Metalloprotease Inhibitors
  申请人：STEENECK Christoph

  公开号：US20090312312A1

  公开（公告）日：2009-12-17

  The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP-13 inhibiting and MMP-3 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP-13 and MMP-3 inhibitors.
• Dipeptidyl Peptidase-IV Inhibitors
  申请人：KROTH Heiko

  公开号：US20110112051A1

  公开（公告）日：2011-05-12

  The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.