(S)-2-(2,6-Dichloro-benzoylamino)-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid | 863226-76-0

• 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)-2-(2,6-Dichloro-benzoylamino)-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid
• 英文别名: (2S)-2-[(2,6-dichlorophenyl)formamido]-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydropyridazin-4-yl)phenyl]propanoic acid；(2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(5-methoxy-2-methyl-3-oxopyridazin-4-yl)phenyl]propanoic acid
• CAS: 863226-76-0
• 化学式: C₂₂H₁₉Cl₂N₃O₅
• 分子量: 476.316
• InChiKey: WYHTUAPAMDIATI-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-(2,6-Dichloro-benzoylamino)-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic 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 、 盐酸羟胺 、 三乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 20.08h， 生成 C₂₂H₂₀Cl₂N₄O₅
  参考文献：
  名称：

  Pyridazinones as antagonists of alpha4 integrins

  摘要：

  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。

  公开号：

  US20050192279A1
• 作为产物：
  描述：

  2,6-二氯苯甲酰氯 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 1.17h， 生成 (S)-2-(2,6-Dichloro-benzoylamino)-3-[4-(5-methoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic 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

文献信息

• [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。
• Substituted benzenesulfonamides as inhibitors of alpha-4 beta-7 integrin activity
  申请人：EA PHARMA CO., LTD.

  公开号：US10562898B2

  公开（公告）日：2020-02-18

  Provided is a compound having α4 integrin inhibitory action. The compound is a sulfonamide derivative represented by the following formula (I), or pharmaceutically acceptable salt thereof: where R1 to R5, e to h, D, and B represent those as described in the specification.

  本发明提供了一种具有α4整合素抑制作用的化合物。 该化合物是由下式（I）代表的磺酰胺衍生物，或其药学上可接受的盐： 其中 R1 至 R5、e 至 h、D 和 B 代表说明书中所述的那些。
• 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.
• SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
  申请人：EA PHARMA CO., LTD.

  公开号：US20190040059A1

  公开（公告）日：2019-02-07

  Provided is a compound having α4 integrin inhibitory action. The compound is a sulfonamide derivative represented by the following formula (I), or pharmaceutically acceptable salt thereof: where R 1 to R 5 , e to h, D, and B represent those as described in the specification.
• [EN] INTEGRIN α4β7 INHIBITOR<br/>[FR] INHIBITEUR DE L'INTÉGRINE α4β7<br/>[JA] α４β７インテグリン阻害剤
  申请人：EA PHARMA CO LTD

  公开号：WO2017135471A1

  公开（公告）日：2017-08-10

  優れたα４インテグリン阻害作用を有する化合物を提供すること。　下記一般式（Ｉ）で示されるスルホンアミド誘導体又はその医薬的に許容しうる塩。 （式中、R1～Ｒ５、e～ｈ、Ｄ及びＢは、明細書中に記載された通りである）