4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid | 883969-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid
• 英文别名: 4-[2,4-dichloro-3-(2,4-dimethylquinolin-8-yloxymethyl)benzenesulfonylamino]tetrahydropyrane-4-carboxylic acid；4-[2,4-dichloro-3-(2,4-dimethylquinolin-8-ylmethyl)benzenesulfonylamino]tetrahydropyrane-4-carboxylic acid；4-[[2,4-Dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carboxylic acid
• CAS: 883969-08-2
• 化学式: C₂₄H₂₄Cl₂N₂O₆S
• 分子量: 539.436
• InChiKey: FMBMXBSTAQWTDW-UHFFFAOYSA-N

物化性质

• 沸点：
  736.6±70.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-(4-[4-((S)-2-amino-6-guanidino-hexanoyl)-piperazine-1-carbonyl]tetrahydro-pyran-4-yl)-2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonamide trifluoroacetate salt
  参考文献：
  名称：

  Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine

  摘要：

  A series of alpha,alpha-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B-2(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.036
• 作为产物：
  描述：

  4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid methyl ester 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 4.0h， 以90%的产率得到4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid
  参考文献：
  名称：

  [EN] NON-PEPTIDE BRADYKININ ANTAGONISTS AND PHARMACEUTICAL COMPOSITIONS THEREFROM
  [FR] ANTAGONISTES DE BRADYKININE NON-PEPTIDIQUES ET COMPOSITIONS PHARMACEUTIQUES CONSTITUEES DE CES COMPOSES

  摘要：

  具有作为布雷金肽（BK）B2受体选择性拮抗剂活性的非肽化合物。这些化合物在化学上的特征是存在一个带有环状基团的α-氨基酸取代基和一个四烷基铵基团。

  公开号：

  WO2006040004A1

文献信息

• Non-peptide bradykinin antagonists and pharmaceutical compositions therefrom
  申请人：Felicetti Patrizia

  公开号：US20070281944A1

  公开（公告）日：2007-12-06

  Disclosed are non-peptide compounds having activity as selective antagonists of bradykinin (BK) B2 receptor. The compounds are chemically characterized by the presence of an amino acid alpha substituted with a cyclic group and by a tetraalkylammonium group. Also disclosed are pharmaceutical compositions containing the compound, and methods of using the compounds to treat patients having conditions, disorders or diseases involving activation of bradykinin B2 receptor.

  本发明涉及一种具有选择性拮抗激活剂作用的非肽类化合物，其与布雷地酮（BK）B2受体相互作用。该化合物化学特征在于存在带有环状基团的氨基酸α取代物和四烷基铵基团。此外，还揭示了含有该化合物的制药组合物，并且揭示了使用该化合物治疗患有与布雷地酮B2受体激活有关的疾病、疾病或病情的患者的方法。
• Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 2. Synthesis and Structure−Activity Relationships of α,α-Cycloalkylglycine Sulfonamides
  作者：Daniela Fattori、Cristina Rossi、Christopher I. Fincham、Valerio Caciagli、Fernando Catrambone、Piero D'Andrea、Patrizia Felicetti、Martina Gensini、Elena Marastoni、Rossano Nannicini、Marielle Paris、Rosa Terracciano、Alessandro Bressan、Sandro Giuliani、Carlo A. Maggi、Stefania Meini、Claudio Valenti、Laura Quartara

  DOI：10.1021/jm061143k

  日期：2007.2.8

  Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B-2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.
• J. Med. Chem. 2007, 50, 550-565
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 2006, 49, 3602-3613
  作者：

  DOI：——

  日期：——
• US7645759B2
  申请人：——

  公开号：US7645759B2

  公开（公告）日：2010-01-12