Boc-Aib-(D)-O-2,4-diF-Bn-Ser-OH | 218163-82-7

• 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: Boc-Aib-(D)-O-2,4-diF-Bn-Ser-OH
• 英文别名: 2(R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(2,4-difluoro-benzyloxy)-propionic acid；(2R)-2-([2-[(Tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-3-[(2,4-difluorobenzyl)oxy]propanoic acid；(2R)-3-[(2,4-difluorophenyl)methoxy]-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoic acid
• CAS: 218163-82-7
• 化学式: C₁₉H₂₆F₂N₂O₆
• 分子量: 416.422
• InChiKey: XTDFYWBRBUAIBZ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-Aib-(D)-O-2,4-diF-Bn-Ser-OH 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 乙醇 、 二氯甲烷 为溶剂， 生成 2-amino-N-[1-(R)-(2,4-difluoro-benzyloxymethyl)-2-oxo-2-(3-oxo-3a-(R)-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-2,3,3a,4,6,7-hexahydropyrazolo[4,3-c]pyridin-5-yl)-ethyl]-2-methyl-propionamide
  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 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 Boc-Aib-(D)-O-2,4-diF-Bn-Ser-OH
  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

• Combinations of &bgr;3 agonists and growth hormone secretagogues
  申请人：Pfizer Inc.

  公开号：US06657063B1

  公开（公告）日：2003-12-02

  This invention is directed to pharmaceutical compositions comprising &bgr;3 adrenergic agonists including (4-(2-(2-(6-aminopyridin-3-yl)-2(R)-hydroxyethylamino)ethoxy)phenyl)acetic acid and growth hormone or growth hormone secretagogues, prodrugs thereof or pharmaceutically acceptable salts of said compounds or said prodrugs. The invention is also directed to methods of using those compositions in the treatment of obesity, diabetes, hypertension and frailty in animals and particularly in humans.

  这项发明涉及包括β3肾上腺素受体激动剂在内的药物组合物，其中包括(4-(2-(2-(6-氨基吡啶-3-基)-2(R)-羟乙基氨基)乙氧基)苯乙酸)和生长激素或生长激素促分泌剂，以及这些化合物或其前药的药用可接受盐。该发明还涉及使用这些组合物治疗动物中的肥胖、糖尿病、高血压和衰弱，特别是在人类中的方法。
• 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。
• 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.