(R)-2-tert-Butoxycarbonylamino-3-(3,4-difluoro-benzyloxy)-propionic acid | 616881-82-4

• 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: (R)-2-tert-Butoxycarbonylamino-3-(3,4-difluoro-benzyloxy)-propionic acid
• 英文别名: (2R)-3-[(3,4-difluorophenyl)methoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 616881-82-4
• 化学式: C₁₅H₁₉F₂NO₅
• 分子量: 331.316
• InChiKey: PSOKXXFAOJGECI-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：

  (R)-2-tert-Butoxycarbonylamino-3-(3,4-difluoro-benzyloxy)-propionic acid 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 (R)-2-Amino-3-(3,4-difluoro-benzyloxy)-propionic acid
  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 、 3,4-二氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-2-tert-Butoxycarbonylamino-3-(3,4-difluoro-benzyloxy)-propionic acid
  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

• 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。
• GROWTH HORMONE SECRETAGOGUES
  申请人：ELI LILLY AND COMPANY

  公开号：EP1497316A2

  公开（公告）日：2005-01-19
• L-MALATE SALT OF 2, 7 - DIAZA - SPIRO [4.5]DEC- 7 - YLE DERIVATIVES AND CRYSTALLINE FORMS THEREOF AS GHRELIN RECEPTOR AGONISTS
  申请人：Novartis AG

  公开号：EP2852591A1

  公开（公告）日：2015-04-01