(R)-tert-butyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-ylamino)pyrrolidine-1-carboxylate | 1035097-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (R)-tert-butyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-ylamino)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3R)-3-[[1-(oxan-2-yl)indazol-5-yl]amino]pyrrolidine-1-carboxylate
• CAS: 1035097-04-1
• 化学式: C₂₁H₃₀N₄O₃
• 分子量: 386.494
• InChiKey: XTCSXSDQBZKRDH-DUSLRRAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 (R)-1-Boc-3-氨基吡咯烷 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以65%的产率得到(R)-tert-butyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-ylamino)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Indazoles: Regioselective Protection and Subsequent Amine Coupling Reactions

  摘要：

  Indazoles are unselectively protected under strongly basic conditions to give a mixture at N-1 and N-2. Under mildly acidic conditions, regioselective protection at N-2 takes place. Thermodynamic conditions lead to regioselective protection at N-1. This trend applies to various substituted indazoles. Protected 5-bromoindazoles participate in Buchwald reactions with a range of amines to generate novel derivative.

  DOI：

  10.1021/jo9006656

文献信息

• CYTOSKELETAL ACTIVE RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
  申请人：Lampe John W.

  公开号：US20080214614A1

  公开（公告）日：2008-09-04

  The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

  本发明涉及一种合成的细胞骨架活性化合物，其为rho相关蛋白激酶的抑制剂。本发明还涉及包含此类化合物和药用载体的制药组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或病症的方法。在本发明的一个实施例中，该方法治疗增加的眼内压，如原发性开角型青光眼。该方法包括向受体施用公式I或公式II的细胞骨架活性化合物的治疗有效量，其中该量能够影响肌动蛋白相互作用，例如通过导致细胞松弛和细胞基质附着的改变。
• US8071779B2
  申请人：——

  公开号：US8071779B2

  公开（公告）日：2011-12-06
• US8604205B2
  申请人：——

  公开号：US8604205B2

  公开（公告）日：2013-12-10
• US8604218B2
  申请人：——

  公开号：US8604218B2

  公开（公告）日：2013-12-10
• Indazoles: Regioselective Protection and Subsequent Amine Coupling Reactions
  作者：David J. Slade、Nicholas F. Pelz、Wanda Bodnar、John W. Lampe、Paul S. Watson

  DOI：10.1021/jo9006656

  日期：2009.8.21

  Indazoles are unselectively protected under strongly basic conditions to give a mixture at N-1 and N-2. Under mildly acidic conditions, regioselective protection at N-2 takes place. Thermodynamic conditions lead to regioselective protection at N-1. This trend applies to various substituted indazoles. Protected 5-bromoindazoles participate in Buchwald reactions with a range of amines to generate novel derivative.