D-2-amino-5-phenylpentanoic acid ethyl ester hydrochloride

• 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: D-2-amino-5-phenylpentanoic acid ethyl ester hydrochloride
• 英文别名: 2-amino-5-phenylpentanoic acid ethyl ester hydrochloride；Ethyl (R)-2-amino-5-phenylpentanoate HCl；ethyl (2R)-2-amino-5-phenylpentanoate;hydrochloride
• 化学式: C₁₃H₁₉NO₂*ClH
• 分子量: 257.76
• InChiKey: WOOKDZRTHXBTJE-UTONKHPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  D-2-amino-5-phenylpentanoic acid ethyl ester hydrochloride 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 醋酸异丙酯 、 水 为溶剂， 反应 23.0h， 生成 [1-((R)-1-{[5-(4-Chloro-phenyl)-3,3-dimethyl-1,1-dioxo-2,3-dihydro-1H-1λ⁶-isothiazol-4-ylmethyl]-ethyl-carbamoyl}-4-phenyl-butylcarbamoyl)-1-methyl-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues

  摘要：

  A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.070
• 作为产物：
  描述：

  (+/-)-2-Acetamino-5-phenyl-valeriansaeure 在 acylase I from Aspergillus melleus 盐酸 、 氢氧化钾 、 potassium chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 46.0h， 生成 D-2-amino-5-phenylpentanoic acid ethyl ester hydrochloride
  参考文献：
  名称：

  Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues

  摘要：

  A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.070

文献信息

• Growth hormone secretagogues
  申请人：Eli Lilly and Company

  公开号：US06828331B1

  公开（公告）日：2004-12-07

  What is disclosed are growth hormone secretagogues, and their uses, of the formula wherein R1 is C6H5CH2OCH2—, C6H5 (CH2)3— or indol-3-ylmethyl; Y is pyrrolidin-1-yl, 4-C1-C6 alkylpiperidin-1-yl or NR2R2; R2 are each independently a C1 to C6 alkyl; R3 is 2-napthyl or phenyl para-substituted by W; W is H, F, CF3, C1-C6 alkoxy or phenyl; and R4 is H or CH3, or a pharmaceutically acceptable salt or solvate thereof.

  揭示的是生长激素促分泌素及其用途的公式，其中R1为C6H5CH2OCH2—，C6H5(CH2)3—或吲哚-3-基甲基；Y为吡咯烷-1-基，4-C1-C6烷基哌啶-1-基或NR2R2；R2各自独立为C1到C6烷基；R3为2-萘基或对位由W取代的苯基；W为H，F，CF3，C1-C6烷氧基或苯基；R4为H或CH3，或其药用可接受的盐或溶剂。
• [EN] STEREOSELECTIVE PROCESS FOR THE SYNTHESIS OF (D)-2-AMINO-5-PHENYLPENTANOIC OR ALKYL ESTER THEREOF<br/>[FR] PROCESSUS STEREOSELECTIF POUR LA SYNTHESE DE (D)-2-AMINO-5-PHENYLPENTANOIQUE OU DE L'ESTER ALKYLIQUE DE CELUI-CI
  申请人：LILLY CO ELI

  公开号：WO2003087036A1

  公开（公告）日：2003-10-23

  The present invention provides a process for preparing a compound of formula (I); wherein R is a C1-C6 alkyl; or a salt thereof; comprising:(c) hydrolyzing (D,L)-N-acetyl-2-amino-5-phenylpentanoic acid with a suitable base in the presence of D-aminoacylase to provide (D)-2-amino-5-phenylpentanoic acid; and (d) esterifying (D)-2-amino-5-phenylpentanoic acid with an alkanol. In a further embodiment, the present invention provides a process for selectively preparing (D)-2-amino-5-phenylpentanoic acid comprising hydrolyzing (D,L)-N-acetyl-2-amino-5-phenyl pentanoic acid with a suitable base in the presence of D-aminoacylase. In a still further embodiment, the present invention provides an improved process for preparing a growth hormone secretagogue compound of formula (II) disclosed herein.

  本发明提供了一种制备式(I)化合物的方法；其中R是C1-C6烷基；或其盐；包括：(c)在D-氨基酰化酶存在下，用适当的碱水解(D,L)-N-乙酰-2-氨基-5-苯基戊酸，得到(D)-2-氨基-5-苯基戊酸；和(d)用烷醇酯化(D)-2-氨基-5-苯基戊酸。在另一实施例中，本发明提供了一种选择性制备(D)-2-氨基-5-苯基戊酸的方法，包括在D-氨基酰化酶存在下，用适当的碱水解(D,L)-N-乙酰-2-氨基-5-苯基戊酸。在另一实施例中，本发明提供了一种改进的制备式(II)生长激素促分泌剂化合物的方法。
• Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues
  作者：Britta Evers、Gerd Ruehter、Martina Berg、Jeffrey A. Dodge、Dirk Hankotius、Ulrike Hary、Louis N. Jungheim、Hans-Juergen Mest、Eva-Maria Martin de la Nava、Michael Mohr、Brian S. Muehl、Soenke Petersen、Birgit Sommer、Grit Riedel-Herold、Mark J. Tebbe、Kenneth J. Thrasher、Silke Voelkers

  DOI：10.1016/j.bmc.2005.07.070

  日期：2005.12

  A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative. (c) 2005 Elsevier Ltd. All rights reserved.