O-(2,4-Difluorobenzyl)-D-serine | 218163-80-5

• 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: O-(2,4-Difluorobenzyl)-D-serine
• 英文别名: (2R)-2-amino-3-[(2,4-difluorophenyl)methoxy]propanoic acid
• CAS: 218163-80-5
• 化学式: C₁₀H₁₁F₂NO₃
• 分子量: 231.199
• InChiKey: IECZWLZIRMQBQY-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-(2,4-Difluorobenzyl)-D-serine 在 N-羟基-7-氮杂苯并三氮唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 tert-butyl N-[1-[[(2R)-1-[(3aR)-3-oxo-3a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]-3-[(2,4-difluorophenyl)methoxy]-1-oxopropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Discovery and biological characterization of capromorelin analogues with extended half-lives

  摘要：

  New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma lGF-1 levels. Compounds 4c and 4d (ACD LogD values greater than or equal to2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED(50)s > 10 mg/kg). A less lipophilic derivative 4 (ACD LogD = 1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00734-5
• 作为产物：
  描述：

  2,4-二氟溴苄 在 盐酸 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 O-(2,4-Difluorobenzyl)-D-serine
  参考文献：
  名称：

  Discovery and biological characterization of capromorelin analogues with extended half-lives

  摘要：

  New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma lGF-1 levels. Compounds 4c and 4d (ACD LogD values greater than or equal to2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED(50)s > 10 mg/kg). A less lipophilic derivative 4 (ACD LogD = 1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00734-5

文献信息

• Process for preparing growth hormone secretagogues
  申请人：——

  公开号：US20020002283A1

  公开（公告）日：2002-01-03

  This invention relates to improved processes for preparing compounds of Formula II, 1 and compounds of Formula III, 2 wherein R 1 , R 2 , R 3 and Prt are defined as set forth in the specification.

  这项发明涉及改进的制备公式II的化合物和公式III的化合物的过程，其中R1、R2、R3和Prt的定义如规范中所述。
• Process for the preparation of pyrazolopyridine tartrates
  申请人：Pfizer Products Inc.

  公开号：EP1449842A1

  公开（公告）日：2004-08-25

  This invention relates to a multistep process for the preparation of an L-tartrate salt of formula XX which is an intermediate in the preparation of growth hormone secretagogues.

  本发明涉及一种制备式 XX 的 L-酒石酸盐的多步骤工艺，该 L-酒石酸盐是制备生长激素促泌剂的中间体。
• US6541634B2
  申请人：——

  公开号：US6541634B2

  公开（公告）日：2003-04-01
• US6673929B2
  申请人：——

  公开号：US6673929B2

  公开（公告）日：2004-01-06
• Discovery and biological characterization of capromorelin analogues with extended half-lives
  作者：Philip A. Carpino、Bruce A. Lefker、Steven M. Toler、Lydia C. Pan、John R. Hadcock、Marianne C. Murray、Ewell R. Cook、Joseph N. DiBrino、Shari L. DeNinno、Kristin L. Chidsey-Frink、William A. Hada、John Inthavongsay、Sharon K. Lewis、F.Michael Mangano、Michelle A. Mullins、David F. Nickerson、Oicheng Ng、Christine M. Pirie、John A. Ragan、Colin R. Rose、David A. Tess、Ann S. Wright、Li Yu、Michael P. Zawistoski、John C. Pettersen、Paul A. DaSilva-Jardine、Theresa C. Wilson、David D. Thompson

  DOI：10.1016/s0960-894x(02)00734-5

  日期：2002.11

  New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma lGF-1 levels. Compounds 4c and 4d (ACD LogD values greater than or equal to2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED(50)s > 10 mg/kg). A less lipophilic derivative 4 (ACD LogD = 1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty. (C) 2002 Elsevier Science Ltd. All rights reserved.