(2R)-N-[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-N-methyl-2-(methylamino)-3-(4-phenylphenyl)propanamide | 1026855-58-2

• 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-(4-phenylphenyl)propanamide
• CAS: 1026855-58-2
• 化学式: C₃₁H₃₇N₃O₃
• 分子量: 499.653
• InChiKey: KGXMRMGSNFSPIF-FQLXRVMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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-(4-phenylphenyl)propanamide 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)-4-(1-Aminocyclobutyl)but-2-enoic acid N-((1R)-1-{N-[(1R)-1-benzyl-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(biphenyl-4-yl)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-(4-phenylphenyl)propanamide
  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

• METHOD OF STIMULATING THE MOTILITY OF THE GASTROINTESTINAL SYSTEM USING GROWTH HORMONE SECRETAGOGUES
  申请人：Sapphire Therapeutics, Inc.

  公开号：EP1789067A2

  公开（公告）日：2007-05-30
• Use of growth hormone secretagogues for stimulating the motility of the gastrointestinal system
  申请人：Helsinn Healthcare S.A.

  公开号：EP1789067B8

  公开（公告）日：2012-08-15
• METHOD OF TREATING CELL PROLIFERATIVE DISORDERS USING GROWTH HORMONE SECRETAGOGUES
  申请人：Helsinn Therapeutics (U.S.), Inc.

  公开号：EP2134341A2

  公开（公告）日：2009-12-23
• 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] METHOD OF STIMULATING THE MOTILITY OF THE GASTROINTESTINAL SYSTEM USING GROWTH HORMONE SECRETAGOGUES<br/>[FR] METHODE DE STIMULATION DE LA MOTILITE DU SYSTEME GASTRO-INTESTINAL A L'AIDE DE SECRETAGOGUES D'HORMONES DE CROISSANCE
  申请人：SAPPHIRE THERAPEUTICS INC

  公开号：WO2006020930A2

  公开（公告）日：2006-02-23

  The present invention relates to a method of stimulating the motility of the gastrointestinal system in a subject in need thereof, wherein the subject suffers from maladies (i.e., disorders or diseases) of the gastrointestinal system. The method comprises administering to a subject in need thereof a therapeutically effective amount of a growth hormone secretagogue compound or a pharmaceutically acceptable salt, hydrate or solvate thereof. The growth hormone secretagogue can be co-administered with a laxative, a H2 receptor antagonist, a serotonin 5-HT4 agonist, an antacid, an opioid antagonist, a proton pump inhibitor, a motilin receptor agonist, dopamine antagonist, a cholinergic agonist, a cholinesterase inhibitor, somatostatin, octreotide, or any combination thereof.