(2R)-N-[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-N-methyl-2-(methylamino)-3-naphthalen-2-ylpropanamide | 1026915-42-3

• 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: (2R)-N-[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-N-methyl-2-(methylamino)-3-naphthalen-2-ylpropanamide
• CAS: 1026915-42-3
• 化学式: C₂₉H₃₅N₃O₃
• 分子量: 473.615
• InChiKey: PYJZZQYFVPYYSO-KAYWLYCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-N-[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-N-methyl-2-(methylamino)-3-naphthalen-2-ylpropanamide 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 (2E)-5-Amino-3,5-dimethylhex-2-enoic acid N-((1R)-1-{N-[(1R)-1-benzyl-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylamide
  参考文献：
  名称：

  The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency

  摘要：

  in order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C-max of over 40 ng mL(-1). (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved..

  DOI：

  10.1016/s0223-5234(02)01370-3
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-N-methyl-D-phenylalanine 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 145.99h， 生成 (2R)-N-[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-N-methyl-2-(methylamino)-3-naphthalen-2-ylpropanamide
  参考文献：
  名称：

  The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency

  摘要：

  in order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C-max of over 40 ng mL(-1). (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved..

  DOI：

  10.1016/s0223-5234(02)01370-3

文献信息

• COMPOUNDS WITH GROWTH HORMONE RELEASING PROPERTIES
  申请人：NOVO NORDISK A/S

  公开号：EP1100824B1

  公开（公告）日：2011-03-02
• METHODS OF TREATING OR PREVENTING EMESIS USING GROWTH HORMONE SECRETAGOGUES
  申请人：Helsinn Therapeutics (U.S.), Inc.

  公开号：EP2146732A1

  公开（公告）日：2010-01-27
• [EN] METHODS OF TREATING OR PREVENTING EMESIS USING GROWTH HORMONE SECRETAGOGUES<br/>[FR] PROCÉDÉS DE TRAITEMENT OU DE PRÉVENTION DE VOMISSEMENT METTANT EN OEVRE DES SÉCRÉTAGOGUES D'HORMONES DE CROISSANCE
  申请人：SAPPHIRE THERAPEUTICS INC

  公开号：WO2008124183A1

  公开（公告）日：2008-10-16

  [EN] The present invention relates to methods of treating or preventing emesis and improving a subject's ASAS score by administering to the subject an effective amount of a growth hormone secretagogue compound or a pharmaceutically acceptable salt, hydrate or solvate thereof.
  [FR] La présente invention concerne des procédés de traitement ou de prévention de vomissement et d'amélioration du score ASAS d'un sujet par l'administration au sujet d'une quantité efficace d'un composé à base de sécrétagogues d'hormones de croissance ou un sel, hydrate, ou solvate pharmaceutiquement acceptable de celui-ci.