tert-butyl 4-(5-cyano-1H-indol-3-yl)piperidine-1-carboxylate | 345235-77-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 4-(5-cyano-1H-indol-3-yl)piperidine-1-carboxylate
• 英文别名: 3-[1-(t-butoxycarbonyl)-4-piperidinyl]-5-cyanoindole；3-[1-(t-Butoxycarbonyl)-4-piperidyl]-5-cyanoindole
• CAS: 345235-77-0
• 化学式: C₁₉H₂₃N₃O₂
• 分子量: 325.411
• InChiKey: JYVATAALJBCNCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-cyano-1H-indol-3-yl)piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以91%的产率得到3-(piperidin-4-yl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  Antipsychotic heterocycle compounds

  摘要：

  式I的化合物是有用的抗精神病和抗抑郁药物，表现出对5-HT再摄取和多巴胺D2受体的强效抑制作用。Ar—Y—(CH2)m—Z 在式I中：Ar从1中选择Z为II或III；2Y为硫或氧；R1和R4分别选择自H和较低的烷基；R2、R3、R6和R7分别选择自H、卤素和较低的烷氧基；R5从H、卤素、较低的烷氧基和氰基中选择；m为2-6之间的整数；n为零或整数1或2；虚线代表可选的双键。

  公开号：

  US20020072611A1
• 作为产物：
  描述：

  5-氰基吲哚 在 5%-palladium/activated carbon 、 甲酸铵 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 19.0h， 生成 tert-butyl 4-(5-cyano-1H-indol-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

  摘要：

  Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

  DOI：

  10.1021/ml5001728

文献信息

• Pyrazole-based cathepsin S inhibitors with improved cellular potency
  作者：Jianmei Wei、Barbara A. Pio、Hui Cai、Steven P. Meduna、Siquan Sun、Yin Gu、Wen Jiang、Robin L. Thurmond、Lars Karlsson、James P. Edwards

  DOI：10.1016/j.bmcl.2007.08.038

  日期：2007.10

  High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of Cats inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency, dramatic effects on cellular activity were observed. Optimization afforded indole- and benzothiophene-derived analogues that were high affinity Cats inhibitors (IC50 = 20-40 nM) with good cellular potency (IC50 = 30-340 nM). (c) 2007 Elsevier Ltd. All rights reserved.
• EP1242072A4
  申请人：——

  公开号：EP1242072A4

  公开（公告）日：2004-02-04
• ANTIPSYCHOTIC HETEROCYCLE COMPOUNDS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1242072A1

  公开（公告）日：2002-09-25
• US6476051B2
  申请人：——

  公开号：US6476051B2

  公开（公告）日：2002-11-05
• [EN] ANTIPSYCHOTIC HETEROCYCLE COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLIQUES ANTIPSYCHOTIQUES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2001043740A1

  公开（公告）日：2001-06-21

  Compounds of Formula (I) are useful antipsychotic and antidepressant agents demonstrating potent inhibition of 5-HT reuptake and dopamine D2 receptor antogonism. In Formula (I): Ar is selected from (a) and (b); Z is (II) or (III); Y is sulfur or oxygen; R?1 and R4¿ are independently selected from H and lower alkyl; R?2, R3, R6 and R7¿ are independently selected from H, halogen, and lower alkoxy; R5 is selected from H, halogen, lower alkoxy and cyano; m is an integer from 2-6; n is zero or the integer 1 or 2; and a dotted line represents an optional double bond.