(2R)-N-methyl-2-(methylamino)-N-[(2R)-1-[methyl(piperidin-1-yl)amino]-1-oxo-3-thiophen-2-ylpropan-2-yl]-3-naphthalen-2-ylpropanamide | 232615-48-4

• 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-methyl-2-(methylamino)-N-[(2R)-1-[methyl(piperidin-1-yl)amino]-1-oxo-3-thiophen-2-ylpropan-2-yl]-3-naphthalen-2-ylpropanamide
• CAS: 232615-48-4
• 化学式: C₂₈H₃₆N₄O₂S
• 分子量: 492.685
• InChiKey: WWVHCEMDMHDVCI-CLJLJLNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-N-methyl-2-(methylamino)-N-[(2R)-1-[methyl(piperidin-1-yl)amino]-1-oxo-3-thiophen-2-ylpropan-2-yl]-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， 生成 (2E)-5-Amino-5-methylhex-2-enoic acid N-methyl-N-((1R)-1-(N-methyl-N-[(1R)-1-(N-methyl-N-(piperidin-1-yl)carbamoyl)-2-(thien-2-yl)ethyl]carbamoyl)-2-(2-naphthyl)ethyl)amide
  参考文献：
  名称：

  Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal

  摘要：

  A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00146-x
• 作为产物：
  描述：

  1-methylamino-piperidine 在 哌啶 、 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， 生成 (2R)-N-methyl-2-(methylamino)-N-[(2R)-1-[methyl(piperidin-1-yl)amino]-1-oxo-3-thiophen-2-ylpropan-2-yl]-3-naphthalen-2-ylpropanamide
  参考文献：
  名称：

  Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal

  摘要：

  A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00146-x

文献信息

• Compounds with growth hormone releasing properties
  申请人：NOVO NORDISK A/S

  公开号：EP1506969A1

  公开（公告）日：2005-02-16

  Compounds of the general formula I and their use for treating medical disorders resulting from a deficiency in growth hormone.

  通式 I 的化合物 以及它们在治疗因生长激素缺乏而引起的疾病方面的用途。
• COMPOUNDS WITH GROWTH HORMONE RELEASING PROPERTIES
  申请人：NOVO NORDISK A/S

  公开号：EP1047709B1

  公开（公告）日：2004-11-03
• US6083908A
  申请人：——

  公开号：US6083908A

  公开（公告）日：2000-07-04
• [EN] COMPOUNDS WITH GROWTH HORMONE RELEASING PROPERTIES<br/>[FR] COMPOSES AVEC PROPRIETES DE LIBERATION DE L'HORMONE DE CROISSANCE
  申请人：NOVO NORDISK AS

  公开号：WO1999036431A1

  公开（公告）日：1999-07-22

  Compounds of general formula (I), and their use for treating medical disorders resulting from a deficiency in growth hormone.
• Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal
  作者：Michael Ankersen、Karin Kramer Nielsen、Thomas Kruse Hansen、Kirsten Raun、Birgit Sehested Hansen

  DOI：10.1016/s0223-5234(00)00146-x

  日期：2000.5

  A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. (C) 2000 Editions scientifiques et medicales Elsevier SAS.