2-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester | 876623-95-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (2S)-2-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 876623-95-9
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: ZUESCMOKPVMMFA-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 {2,2-dimethyl-1-[2-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer

  摘要：

  Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.

  DOI：

  10.1021/jm040037k
• 作为产物：
  描述：

  (R)-(-)-1,2,3,4-四氢-1-萘胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.17h， 生成 2-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  IAP BIR domain binding compounds

  摘要：

  本发明揭示了一种化合物的异构体、对映异构体、顺反异构体或互变异构体，该化合物由公式I表示：或其盐，其中R1、R2、R100、R200、A、A1、B、B1、BG、n、Q和Q1是所描述的取代基。本发明还揭示了利用公式1的化合物治疗增殖性疾病的用途。

  公开号：

  US20070093428A1

文献信息

• Tetrapeptide analogs
  申请人：Chao Bin

  公开号：US20100190688A1

  公开（公告）日：2010-07-29

  Compounds, compositions and methods for treatment of hyperproliferative diseases, such as cancer are provided.

  提供了用于治疗过度增殖性疾病，如癌症的化合物、组合物和方法。
• [EN] TETRAPEPTIDE ANALOGS<br/>[FR] ANALOGUES DE TETRAPEPTIDE
  申请人：IDUN PHARMACEUTICALS INC

  公开号：WO2006017295A3

  公开（公告）日：2007-07-12
• [EN] SMALL MOLECULE APOPTOSIS PROMOTERS<br/>[FR] PROMOTEURS D'APOPTOSE DE PETITES MOLÉCULES
  申请人：JOYANT PHARMACEUTICALS INC

  公开号：WO2007136921A3

  公开（公告）日：2008-03-20
• [EN] IAP BIR DOMAIN BINDING COMPOUNDS<br/>[FR] COMPOSÉS DE LIAISON AU DOMAINE IAP BIR
  申请人：AEGERA THERAPEUTICS INC

  公开号：WO2007048224A1

  公开（公告）日：2007-05-03

  [EN] The present disclosure relates to compounds that bind to IAP BIR domains, more particularly the BIR2 and BIR3 domains. The compounds are represented by Formula 1 : (I) These compounds have been found to be useful in altering apoptotic responses in cells which can lead to the treatment of proliferative disorders. Apoptotic pathways are known to play a critical role in the development of cancer, autoimmune disorders and neurodegenerative diseases. A process to make the compounds of Formula 1 is also disclosed.
  [FR] La présente invention concerne des composés qui se lient aux domaines IAP BIR, et particulièrement aux domaines BIR2 et BIR3. Les composés sont représentés par la formule 1 : (I) Ces composés se sont avérés utiles pour modifier des réponses apoptotiques de cellules qui peuvent mener au traitement de troubles prolifératifs. Les voies apoptotiques sont connues pour leur rôle déterminant dans le développement de cancers, de troubles auto-immuns et de maladies neurodégénératives. L'invention concerne également un procédé de fabrication des composés de formule 1.
• Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer
  作者：Thorsten K. Oost、Chaohong Sun、Robert C. Armstrong、Ali-Samer Al-Assaad、Stephen F. Betz、Thomas L. Deckwerth、Hong Ding、Steven W. Elmore、Robert P. Meadows、Edward T. Olejniczak、Andrew Oleksijew、Tilman Oltersdorf、Saul H. Rosenberg、Alexander R. Shoemaker、Kevin J. Tomaselli、Hua Zou、Stephen W. Fesik

  DOI：10.1021/jm040037k

  日期：2004.8.1

  Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.