tert-butyl N-[3-[2-(1-hydroxy-2-methylpropan-2-yl)oxyphenyl]propyl]carbamate | 1047664-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: tert-butyl N-[3-[2-(1-hydroxy-2-methylpropan-2-yl)oxyphenyl]propyl]carbamate
• CAS: 1047664-47-0
• 化学式: C₁₈H₂₉NO₄
• 分子量: 323.433
• InChiKey: APWLYKFMTOJEGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-(2-iodophenoxy)-2-methylpropanoate 在 ammonium hydroxide 、 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 palladium 10% on activated carbon 、 氢气 、 二异丁基氢化铝 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， -78.0~20.0 ℃ 、275.8 kPa 条件下， 反应 2.0h， 生成 tert-butyl N-[3-[2-(1-hydroxy-2-methylpropan-2-yl)oxyphenyl]propyl]carbamate
  参考文献：
  名称：

  Optimization of the Potency and Pharmacokinetic Properties of a Macrocyclic Ghrelin Receptor Agonist (Part I): Development of Ulimorelin (TZP-101) from Hit to Clinic

  摘要：

  High-throughput screening of Tranzyme Pharma's proprietary macrocycle library using the aequorin Ca2+-bioluminescence assay against the human ghrelin receptor (GRLN) led to the discovery of novel ago fists against this G-protein coupled receptor. Early hits such as 1 (K-i = 86 nM, EC50 = 134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization. While such macrocycles are not fully rule-of-five compliant, principally due to their molecular weight and clogP, optimization of their pharmacokinetic properties proved feasible largely through conformational rigidification. Extensive SAR led to the identification of 2 (K-i = 16 nM, EC50 = 29 nM), also known as ulimorelin or TZP-101, which has progressed to phase III human clinical trials for the treatment of postoperative ileus. X-ray structure and detailed NMR studies indicated a rigid peptidomimetic portion in 2 that is best defined as a nonideal type-I' beta-turn. Compound 2 is 24% orally bioavailable in both rats and monkeys. Despite its potency, in vitro and in gastric emptying studies, 2 did not induce growth hormone (GH) release in rats, thus demarcating the GH versus GI pharmacology of GRLN.

  DOI：

  10.1021/jm2007062

文献信息

• MACROCYCLIC GHRELIN RECEPTOR MODULATORS AND METHODS OF USING THE SAME
  申请人：Hoveyda Hamid

  公开号：US20080194672A1

  公开（公告）日：2008-08-14

  The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

  本发明提供了一种新颖的构象定义明确的大环化合物，可以作为生长激素分泌素受体（GHS-R1a及其亚型、异构体和变体）的选择性调节剂。本文还描述了合成这些新型化合物的方法。这些化合物可用作生长激素分泌素受体的激动剂，用于治疗和预防一系列医疗状况，包括但不限于代谢和/或内分泌紊乱、胃肠道紊乱、心血管疾病、肥胖和与肥胖相关的疾病、中枢神经系统疾病、骨骼疾病、遗传疾病、过度增生性疾病和炎症性疾病。
• Macrocyclic ghrelin receptor modulators and methods of using the same
  申请人：Ocera Therapeutics, Inc.

  公开号：US10258602B2

  公开（公告）日：2019-04-16

  The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

  本发明提供了可作为胃泌素受体（生长激素分泌受体，GHS-R1a 及其亚型、同工型和变体）选择性调节剂的构象明确的新型大环化合物。本文还描述了合成这些新型化合物的方法。这些化合物可作为胃泌素受体的激动剂以及治疗和预防一系列疾病的药物，这些疾病包括但不限于代谢和/或内分泌失调、胃肠道疾病、心血管疾病、肥胖和肥胖相关疾病、中枢神经系统疾病、骨骼疾病、遗传性疾病、过度增殖性疾病和炎症性疾病。
• US9371297B2
  申请人：——

  公开号：US9371297B2

  公开（公告）日：2016-06-21
• US9949949B2
  申请人：——

  公开号：US9949949B2

  公开（公告）日：2018-04-24