L-2-(boc-氨基)-3-(4-甲氧基-2-乙基联苯-4-基)丙酸 | 872142-88-6

• 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
• 中文名称: L-2-(boc-氨基)-3-(4-甲氧基-2-乙基联苯-4-基)丙酸
• 英文名称: (S)-2-(tert-butoxycarbonylamino)-3-(2'-ethyl-4'-methoxylbiphenyl-4-yl)propanoic acid
• 英文别名: Boc-4-(4-methoxy-2-ethylphenyl)-L-phenylalanine；(2S)-3-[4-(2-ethyl-4-methoxyphenyl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 872142-88-6
• 化学式: C₂₃H₂₉NO₅
• 分子量: 399.487
• InChiKey: GVYVXRZCXKXMCA-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  L-2-(boc-氨基)-3-(4-甲氧基-2-乙基联苯-4-基)丙酸 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以100%的产率得到(S)-2-amino-3-(2'-ethyl-4'-methoxy-[1,1'-biphenyl]-4-yl)propanoic acid hydrochloride
  参考文献：
  名称：

  Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity

  摘要：

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.

  DOI：

  10.1021/jm900752a
• 作为产物：
  描述：

  (S)-2-(tert-butoxycarbonylamino)-3-(2'-ethyl-4'-methoxylbiphenyl-4-yl)propanoic acid methyl ester 在 甲醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 L-2-(boc-氨基)-3-(4-甲氧基-2-乙基联苯-4-基)丙酸
  参考文献：
  名称：

  Process for the preparation of amino acids useful in the preparation of peptide receptor modulators

  摘要：

  本发明提供了一种有用的过程，用于制备在制备氨基酸时有用的中间体，这些氨基酸在制备肽受体调节剂时非常有用，例如这些肽受体的激动剂或部分激动剂。这种肽受体调节剂包括例如类胰高血糖素样肽-1受体调节剂，对改善糖尿病状况非常有用。

  公开号：

  US20060004222A1

文献信息

• Process for the preparation of amino acids useful in the preparation of peptide receptor modulators
  申请人：Mathur Arvind

  公开号：US20060004222A1

  公开（公告）日：2006-01-05

  The present invention provides process useful for the preparation of intermediates which are useful in the preparation of amino acids useful in preparing peptide receptor modulators, for example agonists or partial agonists of such peptide receptors. Such peptide receptor modulators include, for example glucagon like peptide-1 receptor modulators which are useful for the amelioration of the diabetic condition.

  本发明提供了一种有用的过程，用于制备在制备氨基酸时有用的中间体，这些氨基酸在制备肽受体调节剂时非常有用，例如这些肽受体的激动剂或部分激动剂。这种肽受体调节剂包括例如类胰高血糖素样肽-1受体调节剂，对改善糖尿病状况非常有用。
• N-TERMINALLY MODIFIED GLP-1 RECEPTOR MODULATORS
  申请人：Ewing R. William

  公开号：US20080045461A1

  公开（公告）日：2008-02-21

  The subject matter described herein provides novel human glucagon-like peptide-1 (GLP-1) receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. The described compounds include chemically modified peptides that may stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The disclosed and claimed peptides show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

  本文所述主题提供了新颖的人类胰高血糖素样肽-1（GLP-1）受体调节剂，其生物活性类似或优于天然GLP-1肽，因此可用于治疗或预防与GLP活性相关的疾病或疾病。所述化合物包括化学修饰的肽，可以刺激2型糖尿病患者的胰岛素分泌，但也产生其他有益的胰岛素促分泌反应。这些合成肽GLP-1受体调节剂表现出对蛋白酶解的稳定性增加，使它们成为口服或静脉注射的理想治疗候选药物。所披露和声称的肽显示出理想的药代动力学特性和糖尿病疗效模型的理想效力。
• Sustained release GLP-1 receptor modulators
  申请人：Qian Feng

  公开号：US20070099835A1

  公开（公告）日：2007-05-03

  The present invention provides novel pharmaceutical compositions comprising a human glucagon-like peptide-1 (GLP-1)-receptor modulator as an active ingredient in a sustained release formulation.

  本发明提供了一种新型药物组合物，包括一种人类胰高血糖素样肽-1（GLP-1）受体调节剂作为活性成分，并以缓释制剂的形式进行。
• HUMAN GLUCAGON-LIKE-PEPTIDE-1 MODULATORS AND THEIR USE IN THE TREATMENT OF DIABETES AND RELATED CONDITIONS
  申请人：Ewing William R.

  公开号：US20080242593A1

  公开（公告）日：2008-10-02

  The present invention provides novel human glucagon-like peptide-1 (GLP-1)-receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The peptides of this invention show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

  本发明提供了新型的人类胰高血糖素样肽-1（GLP-1）受体调节剂，其生物活性类似或优于天然GLP-1肽，因此可用于治疗或预防与GLP活性相关的疾病或障碍。此外，本发明提供了新型的化学修饰肽，不仅能刺激2型糖尿病患者的胰岛素分泌，还能产生其他有益的胰岛素促进反应。这些合成肽GLP-1受体调节剂具有较高的蛋白酶水解稳定性，使其成为口服或静脉注射的理想治疗候选药物。本发明的肽具有理想的药代动力学特性和糖尿病疗效模型的理想效力。
• N-terminally modified GLP-1 receptor modulators
  申请人：Ewing R. William

  公开号：US20070021346A1

  公开（公告）日：2007-01-25

  The subject matter described herein provides novel human glucagon-like peptide-1 (GLP-1) receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. The described compounds include chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The disclosed and claimed peptides show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

  本文所描述的主题提供了一种新颖的人类胰高血糖素样肽-1（GLP-1）受体调节剂，其生物活性类似或优于天然GLP-1肽，因此可用于治疗或预防与GLP活性相关的疾病或障碍。所描述的化合物包括化学修饰的肽，不仅能够刺激II型糖尿病患者的胰岛素分泌，还产生其他有益的胰岛素促进反应。这些合成肽GLP-1受体调节剂表现出对蛋白酶水解的稳定性增加，使它们成为口服或静脉注射的理想治疗候选药物。所披露和要求的肽具有理想的药代动力学特性和糖尿病疗效模型中的理想效力。