(R)-3-ethoxy-2-hydroxy-3-oxopropan-1-amine hydrochloride | 133268-49-2

• 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: (R)-3-ethoxy-2-hydroxy-3-oxopropan-1-amine hydrochloride
• 英文别名: (R)-isoserine ethyl ester hydrochloride；ethyl (2R)-3-amino-2-hydroxypropanoate;hydrochloride
• CAS: 133268-49-2
• 化学式: C₅H₁₁NO₃*ClH
• 分子量: 169.608
• InChiKey: KGKMAIHFPSUMHA-PGMHMLKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.71
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  72.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-3-ethoxy-2-hydroxy-3-oxopropan-1-amine hydrochloride 、 4-[1-(cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以99%的产率得到(R)-3-{4-[1-(4-cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599
• 作为产物：
  描述：

  乙醇 、 (R)-异丝氨酸 在 氯化亚砜 作用下， 生成 (R)-3-ethoxy-2-hydroxy-3-oxopropan-1-amine hydrochloride
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599

文献信息

• [EN] SUBSTITUTED PYRIMIDINES AS INHIBITORS OF HIF PROLYL HYDROXYLASE<br/>[FR] PYRIMIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE HIF PROLYL HYDROXYLASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016057762A1

  公开（公告）日：2016-04-14

  The present invention concerns compounds of Formula I that inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced endogenous production of erythropoietin such as anemia and like conditions, as well as pharmaceutical compositions comprising such a compound and a pharmaceutical carrier.

  本发明涉及一种化合物，其化学式为I，能够抑制HIF prolyl羟基化酶，用于增强内源性促红细胞生成素的产生，并用于治疗与内源性促红细胞生成素减少相关的疾病，如贫血等疾病，以及包含此类化合物和药用载体的药物组合物。
• Glucagon antagonists/inverse agonists
  申请人：——

  公开号：US20040024045A1

  公开（公告）日：2004-02-05

  A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism, such as dyslipidemia, and obesity.

  一种新型化合物，能够拮抗胰高血糖素在胰高血糖素受体上的作用。由于这些化合物能够拮抗胰高血糖素受体的作用，因此它们可能适用于治疗和/或预防任何需要拮抗胰高血糖素作用有益的疾病和疾病，例如高血糖症，1型糖尿病，2型糖尿病，脂质代谢紊乱，如血脂异常和肥胖症。
• SUBSTITUTED PYRIMIDINES AS INHIBITORS OF HIF PROLYL HYDROXYLASE
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3204363A1

  公开（公告）日：2017-08-16
• [EN] SUBSTITUTED PYRIMIDINES AS INHIBITORS OF HIF PROLYL HYDROXYLASE<br/>[FR] PYRIMIDINES SUBSTITUÉES UTILISÉES COMME INHIBITEURS DE LA HIF PROLYL HYDROXYLASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016054804A1

  公开（公告）日：2016-04-14

  The present invention concerns compounds of Formula I that inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced endogenous production of erythropoietin such as anemia and like conditions, as well as pharmaceutical compositions comprising such a compound and a pharmaceutical carrier.
• Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor
  作者：János T. Kodra、Anker Steen Jørgensen、Birgitte Andersen、Carsten Behrens、Christian Lehn Brand、Inger Thøger Christensen、Mette Guldbrandt、Claus Bekker Jeppesen、Lotte B. Knudsen、Peter Madsen、Erica Nishimura、Christian Sams、Ulla G. Sidelmann、Raymon A. Pedersen、Francis C. Lynn、Jesper Lau

  DOI：10.1021/jm7015599

  日期：2008.9.11

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.