N-[4-[(1S)-1-[3,5-二甲基-4-[4-(三氟甲基)-1H-吡唑-1-基]苯氧基]丁基]苯甲酰基]-beta-丙氨酸 | 1393124-08-7

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: N-[4-[(1S)-1-[3,5-二甲基-4-[4-(三氟甲基)-1H-吡唑-1-基]苯氧基]丁基]苯甲酰基]-beta-丙氨酸
• 英文名称: (S)-3-(4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzamido)propanoic acid
• 英文别名: Pf-06291874；3-[[4-[(1S)-1-[3,5-dimethyl-4-[4-(trifluoromethyl)pyrazol-1-yl]phenoxy]butyl]benzoyl]amino]propanoic acid
• CAS: 1393124-08-7
• 化学式: C₂₆H₂₈F₃N₃O₄
• 分子量: 503.521
• InChiKey: IBDYYOQKQCCSDP-QFIPXVFZSA-N

物化性质

• 沸点：
  675.0±55.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：50mg/mL；二甲基亚砜：50 mg/ml； DMSO:PBS (pH 7.2) (1:1)：0.5mg/mL；乙醇：0.5 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存于室温环境中，应保持干燥并密封保存。

制备方法与用途

Glucagon receptor antagonists-4 是一个非常有效的胰高血糖素受体拮抗剂。

反应信息

• 作为反应物：
  描述：

  N-[4-[(1S)-1-[3,5-二甲基-4-[4-(三氟甲基)-1H-吡唑-1-基]苯氧基]丁基]苯甲酰基]-beta-丙氨酸 、 (R)-3-(4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzamido)propanoic acid 、 (+/-)-3-(4-(cyclopentyl(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid 、 (R)-3-(4-(cyclopentyl(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzamido)propanoic acid 、 (S)-3-(4-(cyclopentyl(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzamido)propanoic acid 生成 (+/-)-3-(4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzamido)propanoic acid
  参考文献：
  名称：

  Glucagon receptor modulators

  摘要：

  本发明提供了公式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、A1、A2、A3、A4、L、B1、B2、B3和B4的定义如本文所述。发现公式I的化合物可作为胰高血糖素拮抗剂或反向激动剂。因此，公式I的化合物及其药物组合物对于治疗由胰高血糖素介导的疾病、疾病或病况是有用的。

  公开号：

  US08859591B2
• 作为产物：
  描述：

  (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三丁基膦 、 水 、 potassium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 58.0h， 生成 N-[4-[(1S)-1-[3,5-二甲基-4-[4-(三氟甲基)-1H-吡唑-1-基]苯氧基]丁基]苯甲酰基]-beta-丙氨酸
  参考文献：
  名称：

  The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

  摘要：

  A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.014

文献信息

• GLUCAGON RECEPTOR MODULATORS
  申请人：Aspnes Gary Erik

  公开号：US20120202834A1

  公开（公告）日：2012-08-09

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R 1 , R 2 , R 3 , A 1 , A 2 , A 3 , A 4 , L, B 1 , B 2 , B 3 and B 4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.

  本发明提供了一种式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、A1、A2、A3、A4、L、B1、B2、B3和B4如本文所定义。已发现式I的化合物可作为葡萄糖胰高血糖素拮抗剂或逆向激动剂。因此，式I的化合物及其药物组成物对于治疗由葡萄糖胰高血糖素介导的疾病、紊乱或症状是有用的。
• Amide compounds and use thereof
  申请人：ALPHALA CO., LTD.

  公开号：US10882837B2

  公开（公告）日：2021-01-05

  Disclosed are compounds of formula (I) below and pharmaceutically acceptable salts thereof, in which each of variables R1, R2, L, and Z is defined herein. Also disclosed are methods for reducing the glycemic level and treating glucagon-associated disorders with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same.

  公开了下式(I)化合物及其药学上可接受的盐，其中变量R1、R2、L和Z中的每一个在本文中定义。还公开了用式（I）化合物或其盐和含有该化合物的药物组合物降低血糖水平和治疗胰高血糖素相关疾病的方法。
• GLUCAGON RECEPTOR MODULATOR
  申请人：Pfizer Inc.

  公开号：EP2673260B1

  公开（公告）日：2016-08-17
• Methods For Treating Heart Failure Using Glucagon Receptor Antagonists
  申请人：REMD Biotherapeutics, Inc.

  公开号：US20170143673A1

  公开（公告）日：2017-05-25

  The present invention relates to methods for treating or preventing heart failure using a glucagon receptor antagonist or modulator. In various embodiments, the present invention relates to methods for treating post-myocardial infarction heart failure and lateral ventricular (LV) remodeling. In various embodiments, the present invention relates to methods for treating diabetic cardiomyopathy.
• AMIDE COMPOUNDS AND USE THEREOF
  申请人：ALPHALA CO., LTD.

  公开号：US20190345118A1

  公开（公告）日：2019-11-14

  Disclosed are compounds of formula (I) below and pharmaceutically acceptable salts thereof, in which each of variables R 1 , R 2 , L, and Z is defined herein. Also disclosed are methods for reducing the glycemic level and treating glucagon-associated disorders with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same.