6-methylsulfanyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylate-tert-butyl ester | 717842-93-8

• 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: 6-methylsulfanyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylate-tert-butyl ester
• 英文别名: 6-methylsulfanyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester；tert-butyl 6-methylsulfanyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate；tert-butyl 6-methylsulfanyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate
• CAS: 717842-93-8
• 化学式: C₁₇H₂₂N₂O₂S
• 分子量: 318.44
• InChiKey: SDHQHWJEZALIDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 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：
  70.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-methylsulfanyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylate-tert-butyl ester 在 盐酸 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (1R,2R)-N-(1-cyanocyclopropyl)-2-{[6-(methylsulfonyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxamide
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257
• 作为产物：
  描述：

  1-[2-(methylsulfanyl)phenyl]hydrazine 在 盐酸 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 6-methylsulfanyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylate-tert-butyl ester
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257

文献信息

• Novel Compound - 827
  申请人：Dossetter Alexander Graham

  公开号：US20090012077A1

  公开（公告）日：2009-01-08

  The present invention relates to compounds and compositions for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases, including cathepsins B, K, C, F, H, L, O, S, W and X. Of particular interest are diseases associated with Cathepsin K.

  本发明涉及用于治疗与半胱氨酸蛋白酶活性相关疾病的化合物和组合物。这些化合物是半胱氨酸蛋白酶的可逆抑制剂，包括卡特普辛B、K、C、F、H、L、O、S、W和X。特别感兴趣的是与卡特普辛K相关的疾病。
• Substituted tricyclic gamma-carbolines as serotonin receptor agonists and antagonists
  申请人：——

  公开号：US20040180875A1

  公开（公告）日：2004-09-16

  The present invention is directed to novel compounds represented by structural Formula (I): 1 or a pharmaceutically acceptable salt thereof, wherein R 1 , R 4a , R 5 , R 6 , R 7 , R 8 , R 9 , and m, are defined herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain central nervous system disorders. The compounds of this invention are serotonin receptor modulators, in particular 5HT 2C receptor agonists and antagonists, and are useful in the control or prevention of central nervous system disorders including obesity, anorexia, bulemia, depression, anxiety, psychosis, schizophrenia, migraine, addictive behavior, obsessive-compulsive disorder, and sexual disorders.

  本发明涉及由结构式(I)表示的新化合物或其药学上可接受的盐，其中R1、R4a、R5、R6、R7、R8、R9和m在此被定义。本发明还涉及包含这些新化合物作为活性成分的制药配方以及在治疗某些中枢神经系统疾病中使用这些新化合物和它们的配方。本发明的化合物是血清素受体调节剂，特别是5HT2C受体激动剂和拮抗剂，并且在控制或预防中枢神经系统疾病，包括肥胖症、厌食症、暴食症、抑郁症、焦虑症、精神病、精神分裂症、偏头痛、成瘾行为、强迫症和性功能障碍方面是有用的。
• Compound—827
  申请人：AstraZeneca AB

  公开号：US08008279B2

  公开（公告）日：2011-08-30

  The present invention relates to compounds and compositions for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases, including cathepsins B, K, C, F, H, L, O, S, W and X. Of particular interest are diseases associated with Cathepsin K.

  本发明涉及用于治疗与半胱氨酸蛋白酶活性相关的疾病的化合物和组合物。这些化合物是半胱氨酸蛋白酶的可逆抑制剂，包括cathepsins B、K、C、F、H、L、O、S、W和X。特别感兴趣的是与Cathepsin K相关的疾病。
• EP1581221A4
  申请人：——

  公开号：EP1581221A4

  公开（公告）日：2008-11-26
• SUBSTITUTED TRICYCLIC GAMMA-CARBOLINES AS SEROTONIN RECEPTOR AGONISTS AND ANTAGONISTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1581221B1

  公开（公告）日：2011-05-18