| 1180557-35-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1180557-35-0
• 化学式: C₁₆H₂₂O₃S
• 分子量: 294.415
• InChiKey: PHGLGZWKNPDOCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-(azidomethyl)spiro[2.5]octane
  参考文献：
  名称：

  4-Amino-2-cyanopyrimidines: Novel scaffold for nonpeptidic cathepsin S inhibitors

  摘要：

  We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.011
• 作为产物：
  描述：

  螺[2.5]辛-6-基-甲醇 、 对甲苯磺酰氯 在 盐酸 、 三乙胺 、 三甲胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  4-Amino-2-cyanopyrimidines: Novel scaffold for nonpeptidic cathepsin S inhibitors

  摘要：

  We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.011

文献信息

• Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-Cyanopyrimidines. Part 2
  作者：Osamu Irie、Takatoshi Kosaka、Masashi Kishida、Junichi Sakaki、Keiichi Masuya、Kazuhide Konishi、Fumiaki Yokokawa、Takeru Ehara、Atsuko Iwasaki、Yuki Iwaki、Yuko Hitomi、Atsushi Toyao、Hiroki Gunji、Naoki Teno、Genji Iwasaki、Hajime Hirao、Takanori Kanazawa、Keiko Tanabe、Peter C. Hiestand、Marzia Malcangio、Alyson J. Fox、Stuart J. Bevan、Mohammed Yaqoob、Andrew J. Culshaw、Terance W. Hart、Allan Hallett

  DOI：10.1016/j.bmcl.2008.08.067

  日期：2008.10

  We describe here orally active and brain-penetrant cathepsin S selective inhibitors, which are virtually devoid of hERG K(+) channel affinity, yet exhibit nanomolar potency against cathepsin S and over 100-fold selectivity to cathepsin L. The new non-peptidic inhibitors are based on a 2-cyanopyrimidine scaffold bearing a spiro[3.5] non-6-yl-methyl amine at the 4-position. The brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain. (c) 2008 Elsevier Ltd. All rights reserved.