(S)-ethyl 2-(5-(2-amino-3-phenylpropanamido)-3-(pyridin-4-yl)-1H-pyrazol-1-yl)acetate | 1240522-74-0

• 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: (S)-ethyl 2-(5-(2-amino-3-phenylpropanamido)-3-(pyridin-4-yl)-1H-pyrazol-1-yl)acetate
• 英文别名: ethyl 2-[5-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-pyridin-4-ylpyrazol-1-yl]acetate
• CAS: 1240522-74-0
• 化学式: C₂₁H₂₃N₅O₃
• 分子量: 393.445
• InChiKey: ODDKGKBOHCQSLG-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-ethyl 2-(5-(2-amino-3-phenylpropanamido)-3-(pyridin-4-yl)-1H-pyrazol-1-yl)acetate 在 lithium hydroxide monohydrate 、 三乙酰氧基硼氢化钠 作用下， 以 1,4-二氧六环 、 水 、 1,2-二氯乙烷 为溶剂， 反应 13.5h， 生成
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-ethyl 2-(5-(2-amino-3-phenylpropanamido)-3-(pyridin-4-yl)-1H-pyrazol-1-yl)acetate
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854

文献信息

• PHENYLANALINE AMIDE DERIVATIVES USEFUL FOR TREATING INSULIN-RELATED DISEASES AND CONDITIONS
  申请人：Du Xiaohui

  公开号：US20120115811A1

  公开（公告）日：2012-05-10

  Provided herein are compounds of formula I: wherein A, B, X, R 1 , R 2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

  本文所提供的是I式化合物：其中A、B、X、R1、R2和下标n如下所述。本文还提供了包含该化合物的组合物，以及使用它们的方法，例如用于治疗2型糖尿病和2型糖尿病相关疾病的方法。
• Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions
  申请人：Du Xiaohui

  公开号：US08785468B2

  公开（公告）日：2014-07-22

  Provided herein are compounds of formula I: wherein A, B, X, R1, R2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

  本文提供的是I式化合物，其中A、B、X、R1、R2和下标n的定义如下所述。还提供了包含这些化合物的组合物，以及它们的使用方法，例如用于治疗2型糖尿病和2型糖尿病相关疾病。
• [EN] PHENYLALANINE AMIDE DERIVATIVES USEFUL FOR TREATING INSULIN-RELATED DISEASES AND CONDITIONS<br/>[FR] DÉRIVÉS DE LA PHÉNYLALANINE-AMIDE UTILES POUR LE TRAITEMENT DE MALADIES ET ÉTATS LIÉS À L'INSULINE
  申请人：AMGEN INC

  公开号：WO2010093849A3

  公开（公告）日：2010-10-28
• US8785468B2
  申请人：——

  公开号：US8785468B2

  公开（公告）日：2014-07-22
• Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies
  作者：Ming Yu、Mike Lizarzaburu、Alykhan Motani、Zice Fu、Xiaohui Du、Jiwen (Jim) Liu、Xianyun Jiao、SuJen Lai、Peter Fan、Angela Fu、Qingxiang Liu、Michiko Murakoshi、Futoshi Nara、Kozo Oda、Ryo Okuyama、Jeff D. Reagan、Nobuaki Watanabe、Mami Yamazaki、Yumei Xiong、Ying Zhang、Run Zhuang、Daniel C.-H. Lin、Jonathan B. Houze、Julio C. Medina、Leping Li

  DOI：10.1021/ml4000854

  日期：2013.9.12

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.