2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-N-{1-[4-(6-guanidino-hexanoyl)-piperazine-1-carbonyl]-cyclopentyl}benzenesulfonamide

• 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: 2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-N-{1-[4-(6-guanidino-hexanoyl)-piperazine-1-carbonyl]-cyclopentyl}benzenesulfonamide
• 英文别名: 2-[6-[4-[1-[[2,4-Dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-6-oxohexyl]guanidine
• 化学式: C₃₅H₄₅Cl₂N₇O₅S
• 分子量: 746.758
• InChiKey: BQIHVDDBUCQADT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  50
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  182
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-cyclopentanecarboxylic acid 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-N-{1-[4-(6-guanidino-hexanoyl)-piperazine-1-carbonyl]-cyclopentyl}benzenesulfonamide
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 2. Synthesis and Structure−Activity Relationships of α,α-Cycloalkylglycine Sulfonamides

  摘要：

  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.

  DOI：

  10.1021/jm061143k

文献信息

• [EN] BASIC NON-PEPTIDE BRADYKININ ANTAGONISTS AND PHARMACEUTICAL COMPOSITIONS THEREFROM<br/>[FR] ANTAGONISTES DE BRADYKININE NON PEPTIDIQUE DE BASE ET COMPOSITIONS PHARMACEUTIQUES A BASE DESDITS ANTAGONISTES
  申请人：MENARINI RICERCHE SPA

  公开号：WO2003103671A1

  公开（公告）日：2003-12-18

  Non-peptide compounds of formula (I) having activity as specific antagonists of bradykinin (BK) B2 receptor. The compounds are chemically characterized by the presence of an alpha, alpha-disubstituted amino acid at least one amino group, free or salified, or the corresponding ammonium quaternary salt. These BK receptor antagonists are a novel class of medicaments which can be used in all the disorders in which said receptors are involved.

  化学式为(I)的非肽类化合物具有作为布雷金肽(BK) B2受体特异性拮抗剂的活性。这些化合物在化学上的特征是至少有一个氨基团存在α，α-二取代氨基酸，自由或盐化，或相应的铵季铵盐。这些BK受体拮抗剂是一类新型药物，可用于所有涉及该受体的疾病中。
• Basic non-peptide bradykinin antagonists and pharmaceutical compositions therefrom
  申请人：Calvani Federico

  公开号：US20060205712A1

  公开（公告）日：2006-09-14

  Non-peptide compounds of formula (I) having activity as specific antagonists of bradykinin (BK) B2 receptor. The compounds are chemically characterized by the presence of an alpha, alpha-disubstituted amino acid at least one amino group, free or salified, or the corresponding ammonium quaternary salt. These BK receptor antagonists are a novel class of medicaments which can be used in all the disorders in which said receptors are involved

  具有缓激肽（BK）B2 受体特异性拮抗剂活性的式（I）非肽化合物。这些化合物的化学特征是含有至少一个α-α-二取代氨基酸基团（游离的或盐化的）或相应的季铵盐。这些 BK 受体拮抗剂是一类新型药物，可用于治疗所有涉及上述受体的疾病。
• BASIC NON-PEPTIDE BRADYKININ ANTAGONISTS AND PHARMACEUTICAL COMPOSITIONS THEREFROM
  申请人：Menarini Ricerche S.p.A.

  公开号：EP1513531A1

  公开（公告）日：2005-03-16
• US7491825B2
  申请人：——

  公开号：US7491825B2

  公开（公告）日：2009-02-17