N-tert-butoxycarbonylamino-O-(2,4-difluorobenzyl)-D-serine | 218163-79-2

• 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: N-tert-butoxycarbonylamino-O-(2,4-difluorobenzyl)-D-serine
• 英文别名: 2(R)-2-tert-Butoxycarbonylamino-3-(2,4-difluoro-benzyloxy)-propionic acid；(R)-2-tert-Butoxycarbonylamino-3-(2,4-difluoro-benzyloxy)-propionic acid；(R)-2-tert-butoxycarbonylamino-3-(2,4-difluorobenzyloxy)propionic acid；(2R)-3-[(2,4-difluorophenyl)methoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 218163-79-2
• 化学式: C₁₅H₁₉F₂NO₅
• 分子量: 331.316
• InChiKey: CKQVQFMRRVJHAH-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonylamino-O-(2,4-difluorobenzyl)-D-serine 在 盐酸 、 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 、 乙醇 、 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：

  BOC-D-丝氨酸 、 2,4-二氟溴苄 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-tert-butoxycarbonylamino-O-(2,4-difluorobenzyl)-D-serine
  参考文献：
  名称：

  Process for preparing growth hormone secretagogues

  摘要：

  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。

  公开号：

  US20020002283A1

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。
• 3-SPIROCYCLIC PIPERIDINE DERIVATIVES AS GHRELIN RECEPTOR AGONISTS
  申请人：Ambarkhane Ameet Vijay

  公开号：US20120302540A1

  公开（公告）日：2012-11-29

  The invention relates to derivatives of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a disorder or a disease mediated by the ghrelin receptor.

  该发明涉及公式（I）的衍生物，其中取代基如规范中定义；制备这种衍生物的过程；包含这种衍生物的药物组合物；将这种衍生物作为药物；将这种衍生物用于治疗由胃泌素受体介导的疾病或障碍。
• Growth hormone secretagogues
  申请人：Evers Britta

  公开号：US20050240001A1

  公开（公告）日：2005-10-27

  This invention relates to novel compounds which are useful in the modulation of endogenous growth hormone levels in a mammal. The invention further relates to novel intermediates for use in the synthesis of said compounds, as well as novel processes employed in these syntheses. Also included are methods of treating a mammal which include the administration of said compounds.

  本发明涉及一种新型化合物，该化合物在哺乳动物内调节内源性生长激素水平方面具有有用的作用。本发明还涉及用于合成所述化合物的新型中间体，以及用于这些合成的新型工艺。此外，还包括包括给予所述化合物的治疗哺乳动物的方法。
• 3-Spirocyclic Piperidine Derivatives as Ghrelin Receptor Agonists
  申请人：Ambarkhane Ameet Vijay

  公开号：US20130331369A1

  公开（公告）日：2013-12-12

  The invention relates to derivatives of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a disorder or a disease mediated by the ghrelin receptor.

  本发明涉及公式（I）的衍生物，其中取代基如规范中所定义；制备此类衍生物的过程；包括此类衍生物的制药组合物；此类衍生物作为药物；此类衍生物用于治疗由胃饥饿素受体介导的紊乱或疾病。
• 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.