{(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamic acid tert-butyl ester | 1026653-88-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: {(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamic acid tert-butyl ester
• 英文别名: Boc-D-N(Me)2Nal-D-N(Me)Phe-ol；tert-butyl N-[(2R)-1-[[(2R)-1-hydroxy-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-N-methylcarbamate
• CAS: 1026653-88-2
• 化学式: C₂₉H₃₆N₂O₄
• 分子量: 476.616
• InChiKey: BHVMNIBCYKHSSK-CLJLJLNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (alphaR)-alpha-[[(1,1-二甲基乙氧基)羰基]甲基氨基]-2-萘丙酸	(2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propionic acid	147577-61-5	C19H23NO4	329.396

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(R)-N-((R)-1-Hydroxymethyl-2-phenyl-ethyl)-N-methyl-2-methylamino-3-naphthalen-2-yl-propionamide	186840-79-9	C24H28N2O2	376.499
  ——	[3-({(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamoyl)-benzyl]-carbamic acid tert-butyl ester	186841-30-5	C37H43N3O5	609.766

反应信息

• 作为反应物：
  描述：

  {(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamic acid tert-butyl ester 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 20.17h， 生成 [3-({(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamoyl)-benzyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A New Series of Highly Potent Growth Hormone-Releasing Peptides Derived from Ipamorelin

  摘要：

  A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.

  DOI：

  10.1021/jm9801962
• 作为产物：
  描述：

  (alphaR)-alpha-[[(1,1-二甲基乙氧基)羰基]甲基氨基]-2-萘丙酸 、 (2R)-2-(Methylamino)-3-phenylpropan-1-ol 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 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 {(R)-1-[((R)-1-Hydroxymethyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-naphthalen-2-yl-ethyl}-methyl-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A New Series of Highly Potent Growth Hormone-Releasing Peptides Derived from Ipamorelin

  摘要：

  A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.

  DOI：

  10.1021/jm9801962

文献信息

• A New Series of Highly Potent Growth Hormone-Releasing Peptides Derived from Ipamorelin
  作者：Michael Ankersen、Nils L. Johansen、Kjeld Madsen、Birgit S. Hansen、Kirsten Raun、Karin Kramer Nielsen、Henning Thøgersen、Thomas K. Hansen、Bernd Peschke、Jesper Lau、Behrend F. Lundt、Peter H. Andersen

  DOI：10.1021/jm9801962

  日期：1998.9.1

  A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.