(S)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid methyl ester | 862854-54-4

• 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)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid methyl ester
• 英文别名: 2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid methyl ester；methyl (2S)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxopyridazin-4-yl)phenyl]propanoate
• CAS: 862854-54-4
• 化学式: C₁₆H₁₉N₃O₄
• 分子量: 317.345
• InChiKey: PNFJKDUEWPDKMS-LBPRGKRZSA-N

物化性质

• 沸点：
  478.7±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid methyl ester 以 乙腈 为溶剂， 反应 29.0h， 生成 (2S)-2-[(dimethylcarbamoyl)amino]-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydropyridazin-4-yl)phenyl]propanoic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Pyridazinone-Based α₄ Integrin Receptor Antagonists

  摘要：

  A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha(4)beta(1)/VCAM-1 and alpha(4)beta(7)/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the pyridazinone ring as well as the N-acyl phenylalanine scaffold. Potent dual antagonists of alpha(4)beta(1) and alpha(4)beta(7) were generated from an amide subseries; antagonists selective for alpha(4)beta(7) were identified from urea and carbamate-based subseries. The pharmacokinetic properties of selected members of the series have been determined in rats and demonstrate that the use of ester prodrugs and alterations to the amide linkage can lead to improved oral bioavailability in this series. An alpha(4),beta(7)-selective member of the carbamate subseries (36c), upon oral admininstration, demonstrated in vivo efficacy in the mouse DSS colitis model.

  DOI：

  10.1021/jm060031q
• 作为产物：
  描述：

  甲醇 、 (S)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid trifluoroacetic acid salt 在 氯化亚砜 作用下， 反应 2.0h， 生成 (S)-2-amino-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid methyl ester
  参考文献：
  名称：

  [EN] PYRIDAZINONE UREAS AS ANTAGONISTS OF alpha4 INTEGRINS
  [FR] UREES DE PYRIDAZINONE UTILISEES EN TANT QU'ANTAGONISTES DES INTEGRINES DOLLAR G(A)4

  摘要：

  本发明涉及化合物的公式（I），制备这些化合物的方法，组合物，中间体和衍生物，以及用于治疗α4整合素介导的疾病。更具体地说，本发明的吡啶啉酮脲化合物是α4β7整合素抑制剂，可用于治疗整合素介导的疾病。

  公开号：

  WO2005077914A1

文献信息

• Pyridazinones as antagonists of alpha4 integrins
  申请人：Barbay Kent

  公开号：US20050192279A1

  公开（公告）日：2005-09-01

  The present invention relates to certain novel compounds of Formula (I): methods for preparing these compounds, compositions, intermediates and derivatives thereof and for the treatment of integrin mediated disorders.

  本发明涉及某些化合物的新颖结构，其化学式为（I）：制备这些化合物的方法，组合物，中间体及其衍生物以及用于治疗整合素介导的疾病。
• [EN] PYRIDAZINONES AS ANTAGONISTS OF A4 INTEGRINS<br/>[FR] PYRIDAZINONES EN TANT QU'ANTAGONISTES D'INTÉGRINES DOLLAR G(A)4
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005077915A1

  公开（公告）日：2005-08-25

  The present invention relates to certain novel compounds of Formula (I): Formula (I) methods for preparing these compounds, compositions, intermediates and derivatives thereof and for the treatment of integrin mediated disorders.

  本发明涉及某些新型化合物的公式（I）：公式（I）制备这些化合物的方法、组成物、中间体和衍生物以及治疗整合素介导的疾病的方法。
• Bicyclic triazole alpha4 integrin inhibitors
  申请人：Lawson Edward

  公开号：US20060128748A1

  公开（公告）日：2006-06-15

  The compounds of the present invention are novel bicyclic triazole amino acid-derivatives useful as α4 integrin receptor antagonists. The invention is further directed to methods for treating integrin mediated disorders including, but not limited to, inflammatory, autoimmune and cell-proliferative disorders, methods for preparing the compounds and methods for preparing the intermediates, derivatives and pharmaceutical compositions thereof.

  本发明的化合物是一种新型的双环三唑氨基酸衍生物，可用作α4整合素受体拮抗剂。本发明还涉及治疗整合素介导的疾病的方法，包括但不限于炎症、自身免疫和细胞增殖性疾病的方法，制备该化合物的方法以及制备其中间体、衍生物和制药组合物的方法。
• Synthesis and SAR of pyridazinone-substituted phenylalanine amide α4 integrin antagonists
  作者：Yong Gong、J. Kent Barbay、Edward S. Kimball、Rosemary J. Santulli、M. Carolyn Fisher、Alexey B. Dyatkin、Tamara A. Miskowski、Pamela J. Hornby、Wei He

  DOI：10.1016/j.bmcl.2008.01.022

  日期：2008.2

  Structural modi. cation and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide alpha(4) integrin antagonists are described. Functionality requirements for the arylamide moiety and the carboxylic acid group were demonstrated. The study also revealed novel structure - activity relationships (SAR) for arylated pyridazinones. A correlation between bioavailability and permeability was also explored. A selected compound showed effectiveness in a mouse leukocytosis study. (c) 2008 Elsevier Ltd. All rights reserved.
• WO2006/52962
  申请人：——

  公开号：——

  公开（公告）日：——